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Sarrabayrouse G, Joulain C, Bessoles S, Chiron AS, Abina AM, Hacein-Bey-Abina S. Erythropoietin supplementation induces dysbiosis of the gut microbiota and impacts mucosal immunity in a non-diseased mouse model. Front Immunol 2025; 15:1465410. [PMID: 39916952 PMCID: PMC11798978 DOI: 10.3389/fimmu.2024.1465410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 12/20/2024] [Indexed: 02/09/2025] Open
Abstract
A number of drug treatments are known to alter the dialogue between the gut microbiota and the immune system components in the digestive mucosa. Alterations in intestinal homeostasis are now well known to affect peripheral immune responses and favor the occurrence of a number of pathologies such as allergies and cancers. Erythropoietin's known pleiotropic effects might explain the adverse events sometimes observed in anemic patients treated by erythropoiesis-stimulating agents (ESA). However, the impact of this therapeutic cytokine on the homeostasis of the intestinal tract has not previously been investigated in detail. By studying a mouse model of erythropoietin (EPO) supplementation for 28 days, we observed EPO-induced dysbiosis of the fecal microbiota characterized by a greater bacterial load, lower bacterial diversity and taxonomic changes. With regard to the mucosal immune system, an analysis of leukocyte populations in the small intestine and colon treatment revealed low proportions of ileal CD4 lymphocyte subpopulations (Treg, Tr17 and Th17 cells), IgA-secreting plasma cells, and a major macrophage subpopulation, involved in the control of lymphocyte responses. Our results provide for the first time a descriptive analysis of intestinal EPO's regulatory properties and raise questions about the involvement of EPO-induced alterations in the microbiota and the gut immune effectors in the control of intestinal and peripheral immune responses.
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Affiliation(s)
- Guillaume Sarrabayrouse
- Unité des technologies Chimiques et Biologiques pour la Santé, Université Paris Cité, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), UTCBS, Paris, France
| | - Corentin Joulain
- Unité des technologies Chimiques et Biologiques pour la Santé, Université Paris Cité, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), UTCBS, Paris, France
| | - Stéphanie Bessoles
- Unité des technologies Chimiques et Biologiques pour la Santé, Université Paris Cité, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), UTCBS, Paris, France
| | - Andrada S. Chiron
- Unité des technologies Chimiques et Biologiques pour la Santé, Université Paris Cité, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), UTCBS, Paris, France
- Clinical Immunology Laboratory, Groupe Hospitalier Universitaire Paris-Saclay, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Le-Kremlin-Bicêtre, France
| | - Amine M. Abina
- Unité des technologies Chimiques et Biologiques pour la Santé, Université Paris Cité, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), UTCBS, Paris, France
| | - Salima Hacein-Bey-Abina
- Unité des technologies Chimiques et Biologiques pour la Santé, Université Paris Cité, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), UTCBS, Paris, France
- Clinical Immunology Laboratory, Groupe Hospitalier Universitaire Paris-Saclay, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Le-Kremlin-Bicêtre, France
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Alyamany R, Alnughmush A, Alzahrani H, Alfayez M. Let It Grow: The Role of Growth Factors in Managing Chemotherapy-Induced Cytopenia. Curr Oncol 2024; 31:8094-8109. [PMID: 39727719 DOI: 10.3390/curroncol31120596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 12/13/2024] [Accepted: 12/20/2024] [Indexed: 12/28/2024] Open
Abstract
Chemotherapy-induced cytopenia (CIC) is characterized by neutropenia, anemia, and thrombocytopenia, which are common and serious complications in cancer treatment. These conditions affect approximately 60% of patients undergoing chemotherapy and can significantly impact quality of life, treatment continuity, and overall survival. The use of growth factors, including granulocyte colony-stimulating factors (GCSFs), erythropoietin-stimulating agents (ESAs), and thrombopoietin receptor agonists (TPO-RAs), has emerged as a promising strategy for managing CIC. However, the use of these growth factors must be approached with caution. This review provides an overview of the mechanisms, efficacy, and safety of growth factors in the management of CIC. Additionally, we discuss predictive markers for treatment response, potential risks, and highlight areas for future research.
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Affiliation(s)
- Ruah Alyamany
- Department of Hematology, Stem Cell Transplant and Cellular Therapy, Oncology Centre, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia
| | - Ahmed Alnughmush
- Department of Hematology, Stem Cell Transplant and Cellular Therapy, Oncology Centre, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia
| | - Hazzaa Alzahrani
- Department of Hematology, Stem Cell Transplant and Cellular Therapy, Oncology Centre, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia
| | - Mansour Alfayez
- Department of Hematology, Stem Cell Transplant and Cellular Therapy, Oncology Centre, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia
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Zhang C, Cha R, Long K, Liu Y, Dong Y, Zhang Y, Wang X, Jiang X. Functionalized Iron Oxide Nanoparticles for Both Dual-Modal Imaging and Erythropoiesis. ACS APPLIED MATERIALS & INTERFACES 2024; 16:68905-68917. [PMID: 39656520 DOI: 10.1021/acsami.4c15206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2024]
Abstract
Cancer-related anemia (CRA), a complication of cancer, is considered the primary cause of high mortality for cancer patients. Safe and effective theranostics are desirable for realizing the high diagnostic accuracy of tumors and ameliorating CRA in the clinic. However, the available theranostics do not support dual-modal imaging and the amelioration of CRA at the same time. In this study, we synthesized functionalized iron oxide nanoparticles (Fe3O4 NPs) modified with protoporphyrin IX (PPIX) and folic acid (FA) by a one-step modification strategy (Fe3O4@NH-PPIX&FA NPs) or a step-by-step strategy (Fe3O4@NH-PPIX-FA NPs), aiming at both magnetic resonance imaging/fluorescence imaging (MRI/FI) and erythropoiesis. Fe3O4@NH-PPIX-FA NPs displayed better ability of MRI/FI than Fe3O4@NH-PPIX&FA NPs and had an efficient tumor targeting of 45 min after tail vein injection owing to the reduction of the steric effect and extension of FA groups. Fe3O4@NH-PPIX-FA NPs exhibited satisfactory erythropoiesis with up to 20% elevation of red blood cell (RBC) counts and hemoglobin concentrations in mice with CRA, which provided a safe alternative to RBC transfusions, especially for patients needing recurrent RBC transfusions. With excellent performance in both dual-modal imaging and erythropoiesis, Fe3O4@NH-PPIX-FA NPs could be a powerful tool for the theranostics of cancer patients with anemia.
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Affiliation(s)
- Chunliang Zhang
- Laboratory of Theoretical and Computational Nanoscience, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, No. 11 Zhongguancun Beiyitiao, Haidian District, Beijing 100190, P. R. China
- The Ninth Medical Center of PLA General Hospital, No. 9 Anxiang Beili, Chaoyang District, Beijing 100101, P. R. China
| | - Ruitao Cha
- Laboratory of Theoretical and Computational Nanoscience, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, No. 11 Zhongguancun Beiyitiao, Haidian District, Beijing 100190, P. R. China
- NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients, National Institutes for Food and Drug Control, No. 2 Tiantan Xi Li, Dongcheng District, Beijing 100050, P. R. China
| | - Keying Long
- Laboratory of Theoretical and Computational Nanoscience, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, No. 11 Zhongguancun Beiyitiao, Haidian District, Beijing 100190, P. R. China
| | - Yang Liu
- Laboratory of Theoretical and Computational Nanoscience, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, No. 11 Zhongguancun Beiyitiao, Haidian District, Beijing 100190, P. R. China
| | - Yanrong Dong
- Institute of Health Service and Transfusion Medicine, Beijing 100850, P. R. China
| | - Yulong Zhang
- Institute of Health Service and Transfusion Medicine, Beijing 100850, P. R. China
| | - Xiaohui Wang
- Institute of Health Service and Transfusion Medicine, Beijing 100850, P. R. China
| | - Xingyu Jiang
- Guangdong Provincial Key Laboratory of Advanced Biomaterials, Shenzhen Key Laboratory of Smart Healthcare Engineering, Department of Biomedical Engineering, Southern University of Science and Technology, No. 1088 Xueyuan Road, Nanshan District, Shenzhen, Guangdong 518055, P. R. China
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Park HM, Lee J, Lee SY, Kim CH, Kim HR. Intravenous versus oral iron supplementation for iron deficiency anemia in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy: a study protocol for a randomized controlled trial. Trials 2024; 25:771. [PMID: 39548553 PMCID: PMC11566736 DOI: 10.1186/s13063-024-08624-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 11/08/2024] [Indexed: 11/18/2024] Open
Abstract
BACKGROUND Numerous studies have been conducted to manage anemia in surgical patients through iron supplementation as an alternative to blood transfusion. However, patients with locally advanced rectal cancer have often been excluded from these studies, due to their standard treatment involving neoadjuvant chemoradiotherapy. This study aims to evaluate the impact of intravenous versus oral iron supplementation on iron deficiency anemia in patients with rectal cancer receiving preoperative chemoradiotherapy. METHODS This open-label, single-center, parallel, superiority, randomized trial includes patients with primary rectal cancer who are candidates for preoperative chemoradiotherapy and have confirmed iron-deficiency anemia. A total of 94 patients will be randomly assigned in a 1:1 ratio to receive either intravenous or oral iron supplementation. Stratification factors include age (> 70 vs. ≤ 70 years) and baseline serum hemoglobin levels (7-10 g/dL vs. 10-13 g/dL). The primary endpoint is the percentage of patients achieving normalized hemoglobin levels from the start of treatment to the day of admission for surgery. Secondary endpoints include changes in serum hemoglobin from baseline to postoperatively, changes in iron assay parameters, time needed to hemoglobin normalization, volume of blood transfusions required, and incidence of postoperative complications. DISCUSSION This study is the first randomized controlled trial investigating the effect of iron supplementation in iron-deficient patients with rectal cancer undergoing neoadjuvant chemoradiotherapy. This trial is expected to provide evidence for the benefits of administering iron supplementation in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy. TRIAL REGISTRATION Clinical Research Information Service (CRIS) of Republic of Korea, KCT0009260, Registered on March 21, 2024.
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Affiliation(s)
- Hyeung-Min Park
- Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, 322 Seoyang-Ro Hwasun-Eup, Hwasun-Gun, Jeonnam, 58128, Republic of Korea
| | - Jaram Lee
- Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, 322 Seoyang-Ro Hwasun-Eup, Hwasun-Gun, Jeonnam, 58128, Republic of Korea
| | - Soo Young Lee
- Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, 322 Seoyang-Ro Hwasun-Eup, Hwasun-Gun, Jeonnam, 58128, Republic of Korea.
| | - Chang Hyun Kim
- Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, 322 Seoyang-Ro Hwasun-Eup, Hwasun-Gun, Jeonnam, 58128, Republic of Korea.
| | - Hyeong Rok Kim
- Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, 322 Seoyang-Ro Hwasun-Eup, Hwasun-Gun, Jeonnam, 58128, Republic of Korea
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Dear T, Chiu J, Meirovich H, Malkin A, Amjad R, D'Souza D, Callum J, Leung E, Kelly K, Lazo-Langner A, Solh Z. Are outcomes of locally advanced cervical cancer associated with prebrachytherapy hemoglobin values and transfusion practice? An observational study comparing two large academic centres with divergent clinical guidelines. Brachytherapy 2024; 23:660-667. [PMID: 39198044 DOI: 10.1016/j.brachy.2024.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 06/09/2024] [Accepted: 07/31/2024] [Indexed: 09/01/2024]
Abstract
BACKGROUND AND PURPOSE Anemia is common in locally advanced cervical cancer. Clinical practice varies greatly for management of anemia during brachytherapy, with some centres providing red cell transfusion to increase hemoglobin levels above 100 g/L. MATERIALS AND METHODS This is a retrospective observational cohort study of adult patients with cervical cancer treated with brachytherapy at two academic hospitals. One hospital (H1) uses a liberal transfusion strategy with hemoglobin threshold of 100 g/L during brachytherapy and the other uses a restrictive target of 70 g/L (H2). RESULTS Overall, 336 patients met inclusion criteria (H1: 150 patients, H2: 186 patients). 11 patients were excluded (2 at H1, 9 at H2). Demographics at both sites were comparable, except for cancer stage and smoking history. External beam radiation and chemotherapy provided was similar. Hemoglobin values were compared at baseline (within 4 weeks of oncology consult), and prior to the first and second brachytherapy treatments. In total, 101red blood cell (RBC) units were transfused to patients at H1 and 19 units to patients at H2. Patients were followed for a median of 37.0 months (0.6-80.5) at H1, and 33.3 months (1.6-82.0) at H2. There was no significant difference in progression-free or overall survival. Multivariable logistic regression analysis showed that FIGO stage was a predictor for both overall survival and cancer progression. Age, tumor size, chemotherapy, and hemoglobin levels were not predictors of disease progression or mortality. CONCLUSIONS The practice of liberal transfusion should be re-evaluated in the absence of robust data to support its use.
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Affiliation(s)
- Taylor Dear
- Department of Medicine, Division of Hematology, University of Toronto, Toronto, Ontario, Canada
| | - Jodi Chiu
- Department of Medicine, Division of Hematology, Western University, London, Ontario, Canada
| | | | - Amie Malkin
- QUEST Research Program, Toronto, Ontario, Canada; Precision Diagnostics and Therapeutics Program, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Razan Amjad
- Department of Radiation Oncology, King Abdulaziz University, Rabigh, Saudi Arabia; Department of Oncology, Division of Radiation Oncology, Western University, London, Ontario, Canada
| | - David D'Souza
- Department of Oncology, Division of Radiation Oncology, Western University, London, Ontario, Canada
| | - Jeannie Callum
- Department of Pathology and Molecular Medicine, Queen's University, Kingston and Sunnybrook Research Institute, Toronto, Ontario, Canada
| | - Eric Leung
- Department of Oncology, Division of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Kate Kelly
- Department of Medicine, Division of Hematology, Western University, London, Ontario, Canada
| | - Alejandro Lazo-Langner
- Department of Medicine, Division of Hematology, Western University, London, Ontario, Canada
| | - Ziad Solh
- Department of Medicine, Division of Hematology, Western University, London, Ontario, Canada; Department of Pathology and Laboratory Medicine, Transfusion Medicine, Western University, London, Ontario, Canada.
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Chardalias L, Skreka AM, Memos N, Nieri AS, Politis D, Politou M, Theodosopoulos T, Papaconstantinou I. Postoperative Intravenous Iron Infusion in Anemic Colorectal Cancer Patients: An Observational Study. Biomedicines 2024; 12:2094. [PMID: 39335607 PMCID: PMC11428800 DOI: 10.3390/biomedicines12092094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Revised: 09/02/2024] [Accepted: 09/07/2024] [Indexed: 09/30/2024] Open
Abstract
Anemia is the most common extraintestinal symptom of colorectal cancer, with a prevalence of 30-75%. While the preoperative anemia in this patient population has been well studied and its correction 4-6 weeks prior to surgery is recommended when feasible, there is a paucity of data regarding the management of postoperative anemia, which has a prevalence of up to 87% in these patients. To address this issue, we conducted an observational cohort study of surgically treated postoperative anemic patients with colorectal cancer. The objective of this study was to evaluate the effect of intravenous ferric carboxymaltose on the correction of postoperative anemia by postoperative day 30 (POD30). The primary outcome was the change in hemoglobin on POD30, while the secondary outcomes were the change in iron and other laboratory parameters, postoperative complications and transfusions. The results demonstrated that patients treated with intravenous iron exhibited a significant increase in hemoglobin levels by POD30, along with a concomitant increase in hematocrit, ferritin, and transferrin saturation levels, compared to the control group. The findings imply that patients undergoing colorectal cancer surgery with anemia that was not corrected in the preoperative setting may benefit from early postoperative intravenous iron infusion.
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Affiliation(s)
- Leonidas Chardalias
- 2nd Surgical Department, Aretaieion University Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece
| | - Androniki-Maria Skreka
- 2nd Surgical Department, Aretaieion University Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece
| | - Nikolaos Memos
- 2nd Surgical Department, Aretaieion University Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece
| | | | - Dimitrios Politis
- 2nd Surgical Department, Aretaieion University Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece
| | - Marianna Politou
- Hematology Laboratory-Blood Bank, Aretaieion Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece
| | - Theodosios Theodosopoulos
- 2nd Surgical Department, Aretaieion University Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece
| | - Ioannis Papaconstantinou
- 2nd Surgical Department, Aretaieion University Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece
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Tong Z, Xu Z, Duan Y, Sun X, Qi B. The effect of erythropoiesis‑stimulating agents on lung cancer patients: a meta‑analysis. Clin Exp Med 2024; 24:150. [PMID: 38967734 PMCID: PMC11226476 DOI: 10.1007/s10238-024-01391-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 06/05/2024] [Indexed: 07/06/2024]
Abstract
Previous studies have demonstrated that erythropoiesis-stimulating agents (ESAs) can reduce anemia and improve quality of life in cancer patients, but ESAs may increase mortality. Therefore, we conducted a meta-analysis of randomized controlled trials (RCT) comparing the effect and risk of ESAs about the prevention or treatment of anemia in cancer patients. Four databases including PubMed, Embase, Web of science and Cochrane Library were searched for published RCTS on ESAs in the treatment of anemia in lung cancer patients from 2000 to 2023. Endpoints including mortality, incidence of thrombotic vascular events, blood transfusion requirement, and incidence of adverse events. Our meta-analysis included 8 studies, with a sample size of 4240 patients, including 2548 patients in the ESAs group and 1692 patients in the control group. The risk of mortality was lower in patients using ESAs than control group (RR 0.96, 95% CI 0.92-0.99, P = 0.02). But there was no significant difference in the risk of mortality between the patients using ESAs and controls (RR 0.99, 95% CI 0.92-1.06, P = 0.69) after removing Pere 2020. Subgroup analysis found that patients diagnosed with small cell lung cancer (SCLC) (RR 1.00, 95% CI 0.92-1.08, P = 0.16) or non-small cell lung cancer (NSCLC) (RR 1.01, 95% CI 0.87-1.17, P = 0.13) were no significant difference in mortality rate. The thrombotic vascular events increase in patients using ESAs than control group (RR 1.40, 95% CI 1.13-1.72, P = 0.002). The blood transfusion requirement of ESAs group was lower than control group (RR 0.56, 95% CI 0.44-0.72, P < 0.00001). And the subgroups of Darbepoetin alfa (RR 0.57, 95% CI 0.41-0.79, P = 0.003) and Epoetin alfa (RR 0.68, 95% CI 0.47-0.99, P = 0.01) had lower transfusion requirements than the control group. In the SCLC subgroup (RR 0.51, 95% CI 0.40-0.65, P = 0.34), blood transfusion requirements were lower in the ESAs group, but there was no significant difference between the subgroup of patients with NSCLC (RR 0.61, 95% CI 0.36-1.04, P = 0.009). There was no statistically significant difference between the two groups in the incidence of adverse reactions (RR 0.98, 95% CI 0.95-1.00, P = 0.10). In conclusion, ESAs does not increase the mortality of lung cancer patients or may reduce the risk of death, and can reduce the need for blood transfusion, although ESA can increase the incidence of thrombotic vascular adverse events.Registration PROSPERO CRD42023463582.
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Affiliation(s)
- Zhenhua Tong
- Department of Research and Training, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenyang, 110016, China
| | - Zhumeng Xu
- Department of Pharmacy, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yaqi Duan
- Shenyang Pharmaceutical University, Shenyang, Liaoning, China
| | - Xue Sun
- Department of Pharmacy, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenyang, 110016, China.
| | - Bin Qi
- Department of Cardiology, National Key Laboratory of Frigid Zone Cardiovascular Diseases (NKLFZCD), General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenyang, 110016, China.
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Bozzini C, Busti F, Marchi G, Vianello A, Cerchione C, Martinelli G, Girelli D. Anemia in patients receiving anticancer treatments: focus on novel therapeutic approaches. Front Oncol 2024; 14:1380358. [PMID: 38628673 PMCID: PMC11018927 DOI: 10.3389/fonc.2024.1380358] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 03/19/2024] [Indexed: 04/19/2024] Open
Abstract
Anemia is common in cancer patients and impacts on quality of life and prognosis. It is typically multifactorial, often involving different pathophysiological mechanisms, making treatment a difficult task. In patients undergoing active anticancer treatments like chemotherapy, decreased red blood cell (RBC) production due to myelosuppression generally predominates, but absolute or functional iron deficiency frequently coexists. Current treatments for chemotherapy-related anemia include blood transfusions, erythropoiesis-stimulating agents, and iron supplementation. Each option has limitations, and there is an urgent need for novel approaches. After decades of relative immobilism, several promising anti-anemic drugs are now entering the clinical scenario. Emerging novel classes of anti-anemic drugs recently introduced or in development for other types of anemia include activin receptor ligand traps, hypoxia-inducible factor-prolyl hydroxylase inhibitors, and hepcidin antagonists. Here, we discuss their possible role in the treatment of anemia observed in patients receiving anticancer therapies.
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Affiliation(s)
- Claudia Bozzini
- Department of Medicine, Section of Internal Medicine, University of Verona, Verona, Italy
- EuroBloodNet Referral Center, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
| | - Fabiana Busti
- Department of Medicine, Section of Internal Medicine, University of Verona, Verona, Italy
- EuroBloodNet Referral Center, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
| | - Giacomo Marchi
- Department of Medicine, Section of Internal Medicine, University of Verona, Verona, Italy
- EuroBloodNet Referral Center, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
| | - Alice Vianello
- Department of Medicine, Section of Internal Medicine, University of Verona, Verona, Italy
- EuroBloodNet Referral Center, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
| | - Claudio Cerchione
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
| | - Giovanni Martinelli
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
| | - Domenico Girelli
- Department of Medicine, Section of Internal Medicine, University of Verona, Verona, Italy
- EuroBloodNet Referral Center, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
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9
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Migliaccio AR. Erythropoietin: A Personal Alice in Wonderland Trip in the Shadow of the Giants. Biomolecules 2024; 14:408. [PMID: 38672425 PMCID: PMC11047939 DOI: 10.3390/biom14040408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 03/13/2024] [Accepted: 03/20/2024] [Indexed: 04/28/2024] Open
Abstract
The identification of the hormone erythropoietin (EPO), which regulates red blood cell production, and its development into a pharmaceutical-grade product to treat anemia has been not only a herculean task but it has also been the first of its kind. As with all the successes, it had "winners" and "losers", but its history is mostly told by the winners who, over the years, have published excellent scientific and divulgate summaries on the subject, some of which are cited in this review. In addition, "success" is also due to the superb and dedicated work of numerous "crew" members, who often are under-represented and under-recognized when the story is told and often have several "dark sides" that are not told in the polished context of most reviews, but which raised the need for the development of the current legislation on biotherapeutics. Although I was marginally involved in the clinical development of erythropoietin, I have known on a personal basis most, if not all, the protagonists of the saga and had multiple opportunities to talk with them on the drive that supported their activities. Here, I will summarize the major steps in the development of erythropoietin as the first bioproduct to enter the clinic. Some of the "dark sides" will also be mentioned to emphasize what a beautiful achievement of humankind this process has been and how the various unforeseen challenges that emerged were progressively addressed in the interest of science and of the patient's wellbeing.
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10
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Martins-Branco D, Kassapian M, Debien V, Caparica R, Eiger D, Dafni U, Andriakopoulou C, El-Abed S, Ellard SL, Izquierdo M, Vicente M, Chumsri S, Piccart-Gebhart M, Moreno-Aspitia A, Knop AS, Lombard J, de Azambuja E. The impact of erythropoiesis-stimulating agents administration concomitantly with adjuvant anti-HER2 treatments on the outcomes of patients with early breast cancer: a sub-analysis of the ALTTO study. Breast Cancer Res Treat 2024; 203:497-509. [PMID: 37938495 PMCID: PMC11052564 DOI: 10.1007/s10549-023-07159-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 10/05/2023] [Indexed: 11/09/2023]
Abstract
PURPOSE To assess whether erythropoiesis-stimulating agents (ESA) administration impacts the outcomes of patients with HER2-positive early breast cancer (EBC). METHODS ALTTO (NCT00490139) patients were categorized by ESA use during adjuvant anti-HER2 treatment. Disease-free-survival (DFS), overall survival (OS), and time-to-distant recurrence (TTDR) were analyzed by ESA administration, with subgroup analyses according to prognostic factors. Log-rank tests and Cox modeling were performed. Adverse events (AEs) of ESA-interest were compared. RESULTS Among 8381 patients recruited in ALTTO, 123 (1.5%) received ESA concomitantly with study treatment. The median age of patients receiving ESA was 54 years, 39.0% premenopausal, most had tumor size > 2 cm (56.9%), node-positive (58.5%), and positive estrogen receptor expression (61.8%). Median follow-up was shorter in the ESA group [6.1 years (IQR 5.3-7.0) vs. 6.9 years (6.0-7.1); p < 0.001]. There was no DFS difference by ESA administration (log-rank p = 0.70), with 3- and 7-year DFS of 89.2% (95% CI 81.8-93.8%) and 81.6% (71.4-88.5%) in ESA group vs. 88.3% (87.6-89.0%) and 80.0% (79.1-80.9%) in No-ESA group. In subgroup analyses, the interaction of ESA administration with menopausal status was statistically significant (unadjusted p = 0.024; stratified p = 0.033), favoring premenopausal women receiving ESA. We observed no significant association of ESA administration with OS (log-rank p = 0.57; 7-year OS in ESA 88.6% vs. 90.0% in non-ESA) or TTDR. ESA-interest AEs were experienced by eight (6.5%) patients receiving ESA and 417 (5.1%) in the No-ESA group (p = 0.41). CONCLUSION ESA administration to patients receiving adjuvant anti-HER2 treatment for HER2-positive EBC was safe and not associated with a negative impact on survival outcomes.
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Affiliation(s)
- Diogo Martins-Branco
- Academic Trials Promoting Team (ATPT), Institut Jules Bordet, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles (ULB), Rue Meylemeersch, 90, Anderlecht, 1070, Brussels, Belgium
| | | | - Véronique Debien
- Academic Trials Promoting Team (ATPT), Institut Jules Bordet, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles (ULB), Rue Meylemeersch, 90, Anderlecht, 1070, Brussels, Belgium
| | - Rafael Caparica
- Academic Trials Promoting Team (ATPT), Institut Jules Bordet, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles (ULB), Rue Meylemeersch, 90, Anderlecht, 1070, Brussels, Belgium
| | - Daniel Eiger
- Academic Trials Promoting Team (ATPT), Institut Jules Bordet, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles (ULB), Rue Meylemeersch, 90, Anderlecht, 1070, Brussels, Belgium
| | - Urania Dafni
- National and Kapodistrian University of Athens & Frontier Science Foundation-Hellas, Athens, Greece
| | | | | | | | | | - Malou Vicente
- Academic Trials Promoting Team (ATPT), Institut Jules Bordet, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles (ULB), Rue Meylemeersch, 90, Anderlecht, 1070, Brussels, Belgium
| | - Saranya Chumsri
- Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA
| | - Martine Piccart-Gebhart
- Medical Oncology Department, Institut Jules Bordet, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles (ULB), Brussels, Belgium
| | | | - Ann Søegaard Knop
- Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Janine Lombard
- Calvary Mater Hospital & Australia and New Zealand Breast Cancer Trials Group (BCT-ANZ), Newcastle, Australia
| | - Evandro de Azambuja
- Academic Trials Promoting Team (ATPT), Institut Jules Bordet, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles (ULB), Rue Meylemeersch, 90, Anderlecht, 1070, Brussels, Belgium.
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11
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Lederhuber H, Massey LH, Abeysiri S, Roman MA, Rajaretnam N, McDermott FD, Miles LF, Smart NJ, Richards T. Preoperative intravenous iron and the risk of blood transfusion in colorectal cancer surgery: meta-analysis of randomized clinical trials. Br J Surg 2024; 111:znad320. [PMID: 37994900 DOI: 10.1093/bjs/znad320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 07/30/2023] [Accepted: 08/27/2023] [Indexed: 11/24/2023]
Affiliation(s)
- Hans Lederhuber
- Department of Colorectal Surgery, Royal Devon University HealthCare NHS Foundation Trust, Exeter, UK
| | - Lisa H Massey
- Department of Colorectal Surgery, St Mark's the National Bowel Hospital and Academic Institute, London, UK
| | - Sandaruwani Abeysiri
- Institute of Clinical Trials and Methodology, University College London, London, UK
| | - Marius A Roman
- Department of Cardiovascular Sciences and National Institute for Health Research, Leicester, Biomedical Research Unit in Cardiovascular Medicine, College of Life Sciences, University of Leicester, Leicester, UK
| | - Niroshini Rajaretnam
- Department of Colorectal Surgery, Royal Devon University HealthCare NHS Foundation Trust, Exeter, UK
| | - Frank D McDermott
- Department of Colorectal Surgery, Royal Devon University HealthCare NHS Foundation Trust, Exeter, UK
| | - Lachlan F Miles
- Department of Critical Care, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia
| | - Neil J Smart
- Department of Colorectal Surgery, Royal Devon University HealthCare NHS Foundation Trust, Exeter, UK
| | - Toby Richards
- Division of Surgery, University College London, London, UK
- Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia
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12
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Wu T, Tong Z, Ren T, Xie D, Sun X. Effect of erythropoiesis-stimulating agents on breast cancer patients: a meta-analysis. Clin Exp Med 2023; 23:1501-1513. [PMID: 36315312 DOI: 10.1007/s10238-022-00921-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 10/11/2022] [Indexed: 11/03/2022]
Abstract
Erythropoiesis-stimulating agents (ESAs) have been reported to increase the risk of death in cancer patients. In this study, we selected breast cancer, which is currently the most prevalent cancer worldwide, for a meta-analysis to re-examine the advantages and disadvantages of using ESAs. All relevant studies were searched by PubMed, Embase, Web of science, and Cochrane Library. Endpoints including mortality, incidence of thrombo-vascular events, hemoglobin, and transfusion requirements were meta-analyzed based on random-effects model or fixed-effect model. 10 studies were finally included, with a total sample size of 6785 patients. The risk of mortality was higher in patients using ESA than in controls (RR 1.07, 95% CI 1.01-1.13, P = 0.03); subgroup analysis found that the mortality rate was higher in patients treating with ESA for > 6 months (RR 1.27, 95% CI 1.05-1.55, P = 0.01) and epoetin α (RR 1.07, 95% CI 1.01-1.14, P = 0.03). The incidence of thrombo-vascular adverse events was higher in patients using ESA than in controls (RR 1.53, 95% CI 1.27-1.86, P < 0.0001). The ESA group was more effective in improving anemia in cancer patients (MD 1.20, 95% CI 0.77-1.63, P < 0.00001). The blood transfusion needs of patients in the ESA group were significantly lower (RR 0.52, 95%CI 0.44-0.60, P < 0.00001). There was no statistically significant difference between the two groups in disease progression-related conditions (HR 1.03, 95%CI 0.95-1.12, P = 0.52). ESAs increase the risk of mortality and the incidence of thrombo-vascular adverse events in breast cancer patients, while reducing their anemia symptoms and transfusion requirements. Registration PROSPERO CRD42022330450.
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Affiliation(s)
- Tong Wu
- Department of Pharmacy, General Hospital of Northern Theater Command, No.83, Wenhua Road, Shenyang, 110016, China
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China
- University of Chinese Academy of Sciences, 100049, Beijing, China
| | - Zhenhua Tong
- Department of Research and Training, General Hospital of Northern Theater Command, No.83, Wenhua Road, Shenyang, 110016, China
| | - Tianshu Ren
- Department of Pharmacy, General Hospital of Northern Theater Command, No.83, Wenhua Road, Shenyang, 110016, China
| | - Danni Xie
- Department of Pharmacy, General Hospital of Northern Theater Command, No.83, Wenhua Road, Shenyang, 110016, China
| | - Xue Sun
- Department of Pharmacy, General Hospital of Northern Theater Command, No.83, Wenhua Road, Shenyang, 110016, China.
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13
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Vuong KT, Joseph C, Angelo JR. Review of acute kidney injury and progression to chronic kidney disease in pediatric patients undergoing hematopoietic cell transplant. Front Oncol 2023; 13:1161709. [PMID: 37287918 PMCID: PMC10242001 DOI: 10.3389/fonc.2023.1161709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 04/28/2023] [Indexed: 06/09/2023] Open
Abstract
While acute kidney injury (AKI) after hematopoietic cell transplant (HCT) has been well-described in pediatric patients, literature regarding the long term renal consequences of HCT-related AKI, the development of chronic kidney disease (CKD), and CKD care in pediatric patients post-HCT is limited. CKD affects almost 50% of patients after HCT with multifactorial etiology including infection, nephrotoxic medications, transplant-associated thrombotic microangiopathy, graft-versus-host disease, and sinusoidal obstruction syndrome. As renal function declines in CKD, eventually progressing to end stage kidney disease (ESKD), mortality increases and is more than 80% among patients requiring dialysis. Using society guidelines and current literature, this review summarizes definitions and etiologies of and management strategies among patients with AKI and CKD post-HCT with an emphasis on albuminuria, hypertension, nutrition, metabolic acidosis, anemia, and mineral bone disease. The goal of this review is to aid early identification and intervention in patients with renal dysfunction prior to development of ESKD, and to discuss ESKD and renal transplant in these patients post-HCT.
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14
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Dickson EA, Ng O, Keeler BD, Wilcock A, Brookes MJ, Acheson AG. The ICaRAS randomised controlled trial: Intravenous iron to treat anaemia in people with advanced cancer - feasibility of recruitment, intervention and delivery. Palliat Med 2023; 37:372-383. [PMID: 36609173 PMCID: PMC10021128 DOI: 10.1177/02692163221145604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
BACKGROUND Anaemia is highly prevalent in people with advanced, palliative cancer yet sufficiently effective and safe treatments are lacking. Oral iron is poorly tolerated, and blood transfusion offers only transient benefits. Intravenous iron has shown promise as an effective treatment for anaemia but its use for people with advanced, palliative cancer lacks evidence. AIMS To assess feasibility of the trial design according to screening, recruitment, and attrition rates. To evaluate the efficacy of intravenous iron to treat anaemia in people with solid tumours, receiving palliative care. DESIGN A multicentre, randomised, double blind, placebo-controlled trial of intravenous iron (ferric derisomaltose, Monofer®). Outcomes included trial feasibility, change in blood indices, and change in quality of life via three validated questionnaires (EQ5D5L, QLQC30, and the FACIT-F) over 8 weeks. (ISRCTN; 13370767). SETTING/PARTICIPANTS People with anaemia and advanced solid tumours who were fatigued with a performance status ⩽2 receiving support from a specialist palliative care service. RESULTS 34 participants were randomised over 16 months (17 iron, 17 placebo). Among those eligible 47% of people agreed to participate and total study attrition was 26%. Blinding was successful in all participants. There were no serious adverse reactions. Results indicated that intravenous iron may be efficacious at improving participant haemoglobin, iron stores and select fatigue specific quality of life measures compared to placebo. CONCLUSION The trial was feasible according to recruitment and attrition rates. Intravenous iron increased haemoglobin and may improve fatigue specific quality of life measures compared to placebo. A definitive trial is required for confirmation.
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Affiliation(s)
- Edward A Dickson
- National Institute for Health Research
Biomedical Research Centre in Gastrointestinal and Liver Diseases, Nottingham
University Hospitals NHS Trust, Nottingham, UK
- Department of Colorectal Surgery,
Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham,
UK
| | - Oliver Ng
- Department of Colorectal Surgery,
Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham,
UK
| | - Barrie D Keeler
- Milton Keynes University Hospitals NHS
Foundation Trust, Milton Keynes, UK
- The University of Buckingham,
Buckingham, MK18 1EG, UK
| | - Andrew Wilcock
- Department of Palliative Care,
University of Nottingham, Nottingham, UK
| | - Matthew J Brookes
- Department of Gastroenterology, Royal
Wolverhampton NHS Trust, Wolverhampton, UK
- Faculty of Science and Engineering,
University of Wolverhampton, Wolverhampton, UK
| | - Austin G Acheson
- National Institute for Health Research
Biomedical Research Centre in Gastrointestinal and Liver Diseases, Nottingham
University Hospitals NHS Trust, Nottingham, UK
- Department of Colorectal Surgery,
Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham,
UK
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15
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Talboom K, Borstlap WAA, Roodbeen SX, Bruns ERJ, Buskens CJ, Hompes R, Tytgat KMAJ, Tuynman JB, Consten ECJ, Heuff G, Kuiper T, van Geloven AAW, Veldhuis GJ, van der Hoeven JAB, Gerhards MF, Sietses C, Spinelli A, van de Ven AWH, van der Zaag ES, Westerterp M, van Westreenen HL, Dijkgraaf ML, Juffermans NP, Bemelman WA, Hess D, Swank HA, Scholten L, van der Bilt JDW, Jansen MA, van Duijvendijk P, Bezuur D, Carvello M, Foppa C, de Vos tot Nederveen Cappel WH, Geitenbeek RTJ, van Woensel L, De Castro SMM, Wientjes C, van Oostendorp S. Ferric carboxymaltose infusion versus oral iron supplementation for preoperative iron deficiency anaemia in patients with colorectal cancer (FIT): a multicentre, open-label, randomised, controlled trial. Lancet Haematol 2023; 10:e250-e260. [PMID: 36863386 DOI: 10.1016/s2352-3026(22)00402-1] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 11/17/2022] [Accepted: 12/08/2022] [Indexed: 03/03/2023]
Abstract
BACKGROUND A third of patients with colorectal cancer who are eligible for surgery in high-income countries have concomitant anaemia associated with adverse outcomes. We aimed to compare the efficacy of preoperative intravenous and oral iron supplementation in patients with colorectal cancer and iron deficiency anaemia. METHODS In the FIT multicentre, open-label, randomised, controlled trial, adult patients (aged 18 years or older) with M0 stage colorectal cancer scheduled for elective curative resection and iron deficiency anaemia (defined as haemoglobin level of less than 7·5 mmol/L (12 g/dL) for women and less than 8 mmol/L (13 g/dL) for men, and a transferrin saturation of less than 20%) were randomly assigned to either 1-2 g of ferric carboxymaltose intravenously or three tablets of 200 mg of oral ferrous fumarate daily. The primary endpoint was the proportion of patients with normalised haemoglobin levels before surgery (≥12 g/dL for women and ≥13 g/dL for men). An intention-to-treat analysis was done for the primary analysis. Safety was analysed in all patients who received treatment. The trial was registered at ClincalTrials.gov, NCT02243735, and has completed recruitment. FINDINGS Between Oct 31, 2014, and Feb 23, 2021, 202 patients were included and assigned to intravenous (n=96) or oral (n=106) iron treatment. Treatment began a median of 14 days (IQR 11-22) before surgery for intravenous iron and 19 days (IQR 13-27) for oral iron. Normalisation of haemoglobin at day of admission was reached in 14 (17%) of 84 patients treated intravenously and 15 (16%) of 97 patients treated orally (relative risk [RR] 1·08 [95% CI 0·55-2·10]; p=0·83), but the proportion of patients with normalised haemoglobin significantly increased for the intravenous treatment group at later timepoints (49 [60%] of 82 vs 18 [21%] of 88 at 30 days; RR 2·92 [95% CI 1·87-4·58]; p<0·0001). The most prevalent treatment-related adverse event was discoloured faeces (grade 1) after oral iron treatment (14 [13%] of 105), and no treatment-related serious adverse events or deaths were observed in either group. No differences in other safety outcomes were seen, and the most common serious adverse events were anastomotic leakage (11 [5%] of 202), aspiration pneumonia (5 [2%] of 202), and intra-abdominal abscess (5 [2%] 202). INTERPRETATION Normalisation of haemoglobin before surgery was infrequent with both treatment regimens, but significantly improved at all other timepoints following intravenous iron treatment. Restoration of iron stores was feasible only with intravenous iron. In selected patients, surgery might be delayed to augment the effect of intravenous iron on haemoglobin normalisation. FUNDING Vifor Pharma.
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Affiliation(s)
- Kevin Talboom
- Department of Surgery, Amsterdam UMC, Location AMC, Amsterdam, Netherlands
| | | | - Sapho X Roodbeen
- Department of Surgery, Amsterdam UMC, Location AMC, Amsterdam, Netherlands
| | - Emma R J Bruns
- Department of Surgery, Amsterdam UMC, Location AMC, Amsterdam, Netherlands
| | | | - Roel Hompes
- Department of Surgery, Amsterdam UMC, Location AMC, Amsterdam, Netherlands
| | | | - Jurriaan B Tuynman
- Department of Surgery, Amsterdam UMC, Location VUmc, Amsterdam, Netherlands
| | - Esther C J Consten
- Department of Surgery, Meander Medical Centre, Amersfoort, Netherlands; Department of Surgery, University Medical Centre Groningen, Groningen, Netherlands
| | - Gijsbert Heuff
- Department of Surgery, Spaarne Gasthuis, Hoofddorp, Netherlands
| | - Teaco Kuiper
- Department of Gastroenterology, Amstelland Hospital, Amstelveen, Netherlands
| | | | - Gerrit J Veldhuis
- Department of Internal Medicine, Antonius Hospital, Sneek, Netherlands
| | | | - Michael F Gerhards
- Department of Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands
| | - Colin Sietses
- Department of Surgery, Hospital Gelderse Vallei, Ede, Netherlands
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | | | | | | | | | - Marcel L Dijkgraaf
- Epidemiology and Data Science, Amsterdam UMC, location University of Amsterdam, Amsterdam, Netherlands; Amsterdam Public Health Methodology, Amsterdam, Netherlands
| | - Nicole P Juffermans
- Department of Internal Medicine, Amsterdam UMC, Location AMC, Amsterdam, Netherlands
| | - Wilhelmus A Bemelman
- Department of Surgery, Amsterdam UMC, Location AMC, Amsterdam, Netherlands; IBD Unit, Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita Salute San Raffaele, Milan, Italy.
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16
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Dahmen AS, Phuoc VH, Cohen JB, Sexton WJ, Patel SY. Bloodless surgery in urologic oncology: A review of hematologic, anesthetic, and surgical considerations. Urol Oncol 2022; 41:192-203. [PMID: 36470804 DOI: 10.1016/j.urolonc.2022.11.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 11/01/2022] [Accepted: 11/11/2022] [Indexed: 12/03/2022]
Abstract
The urologic oncology patient who refuses blood transfusion can present unique challenges in perioperative blood management. Since blood loss and associated transfusion can be expected in many complex urologic oncology surgeries, a multidisciplinary approach may be required for optimal outcomes. Through collaboration with the hematologist, anesthesiologist, and urologist, various techniques can be employed in the perioperative phases to minimize blood loss and the need for transfusion. We review the risks and benefits of these techniques and offer recommendations specific to the urologic oncology patient.
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Affiliation(s)
- Aaron S Dahmen
- Department of Urology, University of Chicago, Chicago, IL
| | - Vania H Phuoc
- Department of Medical Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL
| | - Jonathan B Cohen
- Department of Anesthesiology, Moffitt Cancer Center and Research Institute, Tampa, FL
| | - Wade J Sexton
- Department of Genitourinary Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL
| | - Sephalie Y Patel
- Department of Anesthesiology, Moffitt Cancer Center and Research Institute, Tampa, FL.
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17
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Chapalain X, Sparrow RL, Aubron C. Research on hemoglobin thresholds for red blood cell transfusion in patients with major oncologic surgery is needed! Transfus Clin Biol 2022; 30:279-281. [PMID: 36460251 DOI: 10.1016/j.tracli.2022.11.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 11/23/2022] [Accepted: 11/23/2022] [Indexed: 12/02/2022]
Affiliation(s)
- Xavier Chapalain
- Department of Anesthesiology and Surgical Intensive Care Unit, Centre Hospitalier Universitaire de Brest, Université de Bretagne Occidentale, Brest, France
| | - Rosemary L Sparrow
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Cécile Aubron
- Department de Médecine Intensive Réanimation, Centre Hospitalier Universitaire de Brest, Université de Bretagne Occidentale, Brest, France; Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), Monash University, Melbourne, Australia.
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18
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Perrone V, Veronesi C, Dovizio M, Ancona DD, Bartolini F, Ferrante F, Lupi A, Palcic S, Re D, Terlizzi AP, Ramirez de Arellano Serna A, Cogliati P, Degli Esposti L. The Influence of Iron-Deficiency Anaemia (IDA) Therapy on Clinical Outcomes and Healthcare Resource Consumptions in Chronic Kidney Disease Patients Affected by IDA: A Real-Word Evidence Study among the Italian Population. J Clin Med 2022; 11:jcm11195820. [PMID: 36233688 PMCID: PMC9573467 DOI: 10.3390/jcm11195820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 09/23/2022] [Accepted: 09/26/2022] [Indexed: 11/16/2022] Open
Abstract
Anaemia is a uraemia-related complication frequently found in non-dialysis-dependent chronic kidney disease (ND-CKD) patients, with iron-deficiency anaemia (IDA) as the main underlying mechanism. Given the suboptimal anaemia management in ND-CKD patients with a co-diagnosis of IDA, this study evaluated the role of IDA therapy on clinical outcomes and healthcare resource consumptions in an Italian clinical setting. A retrospective observational real-world analysis was performed on administrative databases of healthcare entities, covering around 6.9 million health-assisted individuals. From January 2010 to March 2019, ND-CKD patients were included and diagnosed with IDA in the presence of two low-haemoglobin (Hb) measurements. Patients were divided into IDA-treated and untreated, based on the prescription of iron [Anatomical-Therapeutic Chemical (ATC) code B03A] or anti-anaemia preparations (ATC code B03X), and evaluated during a 6-month follow-up from the index date [first low haemoglobin (Hb) detection]. IDA treatment resulted in significantly decreased incidence of all cause-related, cardiovascular-related, and IDA-related hospitalizations (treated vs. untreated: 44.5% vs. 81.8%, 12.3% vs. 25.3%, and 16.2% vs. 26.2%, respectively, p < 0.001). A healthcare direct cost estimation showed that overall mean expenditure per patient reduced by 47% with IDA treatment (5245€ vs. 9918€, p < 0.001), mainly attributable to hospitalizations (3767€ vs. 8486€, p < 0.001). This real-life analysis on Italian ND-CKD-IDA patients indicates that IDA therapy administration provides significant benefits in terms of patients’ clinical outcomes and healthcare cost savings.
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Affiliation(s)
- Valentina Perrone
- CliCon Società Benefit S.r.l. Health, Economics & Outcomes Research, 40137 Bologna, Italy
| | - Chiara Veronesi
- CliCon Società Benefit S.r.l. Health, Economics & Outcomes Research, 40137 Bologna, Italy
| | - Melania Dovizio
- CliCon Società Benefit S.r.l. Health, Economics & Outcomes Research, 40137 Bologna, Italy
| | - Domenica Daniela Ancona
- Dipartimento Farmaceutico, Azienda Sanitaria Locale delle province di Barletta- Andria- Trani (BAT), 76125 Andria, Italy
| | - Fausto Bartolini
- Dipartimento Farmaceutico, Unità Sanitaria Locale Umbria 2, 05100 Terni, Italy
| | - Fulvio Ferrante
- Dipartimento della Diagnostica ed Assistenza Farmaceutica, ASL Frosinone, 03100 Frosinone, Italy
| | - Alessandro Lupi
- Azienda Sanitaria Locale del Verbano Cusio Ossola (VCO), 28887 Omegna, Italy
| | - Stefano Palcic
- Azienda Sanitaria Universitaria Integrata Giuliano-Isontina (ASUGI), 34148 Trieste, Italy
| | - Davide Re
- Dipartimento Assistenza Territoriale, Azienda Sanitaria Locale di Teramo, 64100 Teramo, Italy
| | - Annamaria Pia Terlizzi
- Dipartimento Farmaceutico, Azienda Sanitaria Locale delle province di Barletta- Andria- Trani (BAT), 76125 Andria, Italy
| | | | | | - Luca Degli Esposti
- CliCon Società Benefit S.r.l. Health, Economics & Outcomes Research, 40137 Bologna, Italy
- Correspondence:
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19
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Huang Y, Li M, Lin M, Ou S, Wang J, Huang C, Chou K, Fang H, Lee P, Hsu C, Chen J, Chen H. Erythropoiesis-stimulating agents and incident malignancy in chronic kidney and end-stage renal disease: A population-based study. Clin Transl Sci 2022; 15:2195-2205. [PMID: 35699124 PMCID: PMC9468572 DOI: 10.1111/cts.13353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 04/22/2022] [Accepted: 05/30/2022] [Indexed: 01/25/2023] Open
Abstract
Research investigating incident malignancy risk in erythropoiesis-stimulating agent (ESA) users with chronic kidney disease (CKD) is lacking. We aimed to compare the incident cancer risk between ESA and non-ESA users with CKD or end-stage renal disease (ESRD). In this retrospective cohort study, all adults newly diagnosed with CKD or ESRD between 2000 and 2012 were enrolled. The study population included 98,748 patients. After case-control matching, 7115 patients were included. The defined daily dose (DDD) of ESA was used as the unit for measuring the amount of ESA prescribed. The primary outcome was the risk of incident malignancy. The secondary outcomes were incident malignancy risk in different tertiles of cumulative ESA doses and the risk of different types of cancers. The risk of incident malignancy was 1.84 times higher with ESA treatment than without ESA treatment (hazard ratio, 1.84; 95% confidence interval, 1.43-2.36; p < 0.001). The malignancy risk was positively correlated with the cumulative dose of ESA (p-for-trend = 0.001) and a significant difference in the high annual cumulative DDD cohort (hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.76-3.25; p < 0.001). The risk of genitourinary malignancy was 12.55 times higher with ESA treatment than without ESA treatment (HR, 12.55; 95% CI, 5.78-27.24; p < 0.001). ESA usage is associated with an increased risk of malignancy, particularly genitourinary cancers, in patients with CKD or ESRD. Clinicians should be aware of the occurrence of malignancy, and keep ESA dosage as low as possible.
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Affiliation(s)
- Yu‐Shan Huang
- Department of PediatricsKaohsiung Veterans General HospitalKaohsiungTaiwan
| | - Ming‐Feng Li
- Department of RadiologyKaohsiung Veteran General HospitalKaohsiungTaiwan,Department of Medical ImagingHualien Buddhist Tzu‐Chi General HospitalHualienTaiwan,Department of Medical Imaging and RadiologyShu‐Zen Junior College of Medicine and ManagementKaohsiungTaiwan
| | - Mei‐Chen Lin
- Management Office for Health DataChina Medical University HospitalTaichungTaiwan,College of MedicineChina Medical UniversityTaichungTaiwan
| | - Shih‐Hsiang Ou
- Division of NephrologyDepartment of Internal Medicine, Kaohsiung Veterans General HospitalKaohsiungTaiwan,School of MedicineNational Yang Ming Chiao Tung UniversityTaiwan
| | - Jen‐Hung Wang
- Department of Medical ResearchHualien Buddhist Tzu‐Chi General HospitalHualienTaiwan
| | - Chien‐Wei Huang
- Division of NephrologyDepartment of Internal Medicine, Kaohsiung Veterans General HospitalKaohsiungTaiwan,School of MedicineNational Yang Ming Chiao Tung UniversityTaiwan
| | - Kang‐Ju Chou
- Division of NephrologyDepartment of Internal Medicine, Kaohsiung Veterans General HospitalKaohsiungTaiwan,School of MedicineNational Yang Ming Chiao Tung UniversityTaiwan
| | - Hua‐Chang Fang
- Division of NephrologyDepartment of Internal Medicine, Kaohsiung Veterans General HospitalKaohsiungTaiwan,School of MedicineNational Yang Ming Chiao Tung UniversityTaiwan
| | - Po‐Tsang Lee
- Division of NephrologyDepartment of Internal Medicine, Kaohsiung Veterans General HospitalKaohsiungTaiwan,School of MedicineNational Yang Ming Chiao Tung UniversityTaiwan
| | - Chih‐Yang Hsu
- Division of NephrologyDepartment of Internal Medicine, Kaohsiung Veterans General HospitalKaohsiungTaiwan,School of MedicineNational Yang Ming Chiao Tung UniversityTaiwan
| | - Jin‐Shuen Chen
- Division of NephrologyDepartment of Internal Medicine, Kaohsiung Veterans General HospitalKaohsiungTaiwan
| | - Hsin‐Yu Chen
- Division of NephrologyDepartment of Internal Medicine, Kaohsiung Veterans General HospitalKaohsiungTaiwan,School of MedicineNational Yang Ming Chiao Tung UniversityTaiwan
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Intravenous Iron Supplementation for the Treatment of Chemotherapy-Induced Anemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Clin Med 2022; 11:jcm11144156. [PMID: 35887920 PMCID: PMC9317757 DOI: 10.3390/jcm11144156] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 07/06/2022] [Accepted: 07/08/2022] [Indexed: 02/06/2023] Open
Abstract
Background: The pathophysiology of cancer-related anemia is multifactorial, including that of chemotherapy-induced anemia (CIA). The guidelines are not consistent in their approach to the use of intravenous (IV) iron in patients with cancer as part of the clinical practice. Materials and methods: All randomized controlled trials that compared IV iron with either no iron or iron taken orally for the treatment of CIA were included. We excluded trials if erythropoiesis-stimulating agents (ESAs) were used. The primary outcome was the percentage of patients requiring a red blood cell (RBC) transfusion during the study period. The secondary outcomes included the hematopoietic response (an increase in the Hb level by more than 1 g/dL or an increase above 11 g/dL), the iron parameters and adverse events. For the dichotomous data, risk ratios (RRs) with 95% confidence intervals (Cis) were estimated and pooled. For the continuous data, the mean differences were calculated. A fixed effect model was used, except in the event of significant heterogeneity between the trials (p < 0.10; I2 > 40%), in which we used a random effects model. Results: A total of 8 trials published between January 1990 and July 2021 that randomized 1015 patients fulfilled the inclusion criteria. Of these, 553 patients were randomized to IV iron and were compared with 271 patients randomized to oral iron and 191 to no iron. IV iron decreased the percentage of patients requiring a blood transfusion compared with oral iron (RR 0.72; 95% CI 0.55−0.95) with a number needed to treat of 20 (95% CI 11−100). IV iron increased the hematopoietic response (RR 1.23; 95% CI 1.01−1.5). There was no difference with respect to the risk of adverse events (RR 0.97; 95% CI 0.88−1.07; 8 trials) or severe adverse events (RR 1.09; 95% CI 0.76−1.57; 8 trials). Conclusions: IV iron resulted in a decrease in the need for RBC transfusions, with no difference in adverse events in patients with CIA. IV iron for the treatment of CIA should be considered in clinical practice.
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21
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Zhou QQ, Li J, Liu B, Wang CL. Roxadustat for treatment of anemia in a cancer patient with end-stage renal disease: A case report. World J Clin Cases 2022; 10:6587-6594. [PMID: 35979316 PMCID: PMC9294907 DOI: 10.12998/wjcc.v10.i19.6587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 04/16/2022] [Accepted: 05/08/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Most cancer patients are accompanied by anemia, which will be more serious when combined with end-stage renal disease (ESRD). At present, cancer-related anemia and renal anemia treatments mainly include erythropoiesis-stimulating agents (ESAs), iron supplementation, and blood transfusion, but their effects are often poor with several safety concerns. We have used roxadustat to treat anemia in a cancer patient with ESRD and achieved a successful outcome for the first time.
CASE SUMMARY A 64-year-old man was diagnosed with right renal cancer (clear cell renal cell carcinoma). He did not receive surgery or radiotherapy before admission. He was treated with oral soltan (sunitinib malate) on April 18, 2017. During oral chemotherapy, he had numerous complications, including anemia, hypertension, thyroid hypofunction, skin pigment loss, and renal function deterioration. At last, he progressed to ESRD and began hemodialysis treatment. We initially treated the patient with high-dose ESAs, iron supplementation, adequate dialysis, and even blood transfusion, but his anemia did not improve. Roxadustat is a newly developed drug for renal anemia treatment, but not for cancer-related anemia, let alone to treat anemia in cancer patients with ESRD. We prescribed oral roxadustat to the patient. After a period, his hemoglobin gradually increased. He did not have obvious discomfort symptoms, and his tumor did not progress significantly.
CONCLUSION Oral roxadustat could achieve good results in treating anemia in cancer patients with ESRD.
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Affiliation(s)
- Qiao-Qiao Zhou
- Hemodialysis Room, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610042, Sichuan Province, China
| | - Jing Li
- Hemodialysis Room, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610042, Sichuan Province, China
| | - Bin Liu
- Department of Internal Medicine-Oncology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610042, Sichuan Province, China
| | - Chun-Li Wang
- Hemodialysis Room, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610042, Sichuan Province, China
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22
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Bennett CL, Olivieri N, Hoque S, Aboulafia D, Ventrone A, Lubaczewski C, Dong B, Schooley B, Witherspoon BJ, Ray PS, Hrushesky WJ, Restaino J, Thomsen HS, Mangano D, Mora-Mangano C, McKoy JM, Schoen M, Knopf K, Martin L, Rosen S. Davids versus Goliaths: Pharma and academia threats to individual scientists and clinicians. THE JOURNAL OF SCIENTIFIC PRACTICE AND INTEGRITY 2022. [DOI: 10.35122/001c.36564] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background We previously described experiences of clinicians who published adverse drug reaction reports. We now report on threats and intimidations leveled against clinicians and scientists who received publicly documented threats after communicating safety, efficacy, or data integrity findings contrary to corporate interests. Methods Data on threats and intimidations were obtained from transcripts of governmental hearings or agencies, university-affiliated reports, media interviews, and investigative journalism articles. Content and timing of threats and intimidation, subsequent harms, numbers of persons seriously injured or who died from individual toxicities, financial payments from sponsors related to safety, efficacy, or data integrity concerns, and civil settlements and criminal findings were evaluated. Findings Twenty-six individuals who communicated safety, efficacy, or data integrity concerns were targets of threats and intimidation from corporate employees (twenty-three individuals) or regulatory personnel (three). Seventeen individuals identified instances where pharmaceutical sponsors submitted fraudulent data in support of regulatory approval of a drug or device. Scientist and clinician communications were followed by drug/device withdrawals (fourteen drugs/devices), black box warnings (six drugs), withdrawal of a sponsor’s application for regulatory approval (one device), and delay of approval of a sponsor’s application for regulatory approval (one drug). Actions mainly occurred after persons communicated with pharmaceutical employees (fourteen). Intimidation efforts by corporate personnel included threats of lawsuits (eighteen individuals), hiring private investigators (nine), and public disparagement at conferences (eleven). Related intimidation efforts carried out by academia or regulatory agency superiors included threats of: loss of positions (six), loss of grant funding (two), delays in decisions regarding tenure (two); or reassignment to a low-level position (one). Academic harms included lost: hospital or university appointments (nine and six, respectively), grant funding (two), chairperson title of an international clinical trial group (one), and journal editorial board position (one). Corporate harms included payment of $1 million to defense attorneys in three cases filed against clinicians. Interpretation Threats and intimidation carried out by corporate employees and/or academic supervisors followed public communication of concerns regarding patient safety, drug efficacy, or data integrity, including instances where sponsors were identified as having submitted fraudulent data to regulatory or government agencies. Consideration should be given to filing criminal charges against pharmaceutical executives who are discovered by scientists or clinicians to have knowingly submitted fraudulent data to regulatory or governmental agencies, rather than causing the scientists and clinicians who submit such reports to risk losing their reputations and occupations.
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Affiliation(s)
- Charles L. Bennett
- The City of Hope National Cancer Institute Designated Comprehensive Center, Duarte, California; The SONAR project of the University of South Carolina, College of Pharmacy
| | | | - Shamia Hoque
- The SONAR project of the University of South Carolina
| | | | - Anne Ventrone
- The SONAR project of the University of South Carolina
| | | | - Betty Dong
- The University of California at San Francisco
| | | | | | - Paul S. Ray
- The SONAR project of the University of South Carolina
| | | | - John Restaino
- The SONAR project of the University of South Carolina
| | | | | | | | | | - Martin Schoen
- Saint Louis University; Washington University, School of Medicine
| | - Kevin Knopf
- The SONAR project of the University of South Carolina
| | - Linda Martin
- The SONAR project of the University of South Carolina
| | - Steven Rosen
- The City of Hope National Cancer Institute Designated Comprehensive Center, Duarte, California; The SONAR project of the University of South Carolina, College of Pharmacy
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23
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Lee CT, Lee CC, Wu MJ, Chiu YW, Leu JG, Wu MS, Peng YS, Wu MS, Tarng DC. Long-term safety and efficacy of ferric citrate in phosphate-lowering and iron-repletion effects among patients with on hemodialysis: A multicenter, open-label, Phase IV trial. PLoS One 2022; 17:e0264727. [PMID: 35239732 PMCID: PMC8893642 DOI: 10.1371/journal.pone.0264727] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Accepted: 01/19/2022] [Indexed: 11/30/2022] Open
Abstract
Background We explored the long-term safety and efficacy of ferric citrate in hemodialysis patients in Taiwan, and further evaluated the iron repletion effect and change of iron parameters by different baseline groups. Methods This was a 12-month, Phase IV, multicenter, open-label study. The initial dose of ferric citrate was administered by patients’ clinical condition and further adjusted to maintain serum phosphorus at 3.5–5.5 mg/dL. The primary endpoint was to assess the safety profiles of ferric citrate. The secondary endpoints were to evaluate the efficacy by the time-course changes and the number of subjects who achieved the target range of serum phosphorus. Results A total of 202 patients were enrolled. No apparent or unexpected safety concerns were observed. The most common treatment-emergent adverse events were gastrointestinal-related with discolored feces (41.6%). Serum phosphorus was well controlled, with a mean dose of 3.35±1.49 g/day, ranging from 1.5 to 6.0 g/day. Iron parameters were significantly improved. The change from baseline of ferritin and TSAT were 227.17 ng/mL and 7.53%, respectively (p-trend<0.001), and the increase started to slow down after 3–6 months of treatment. In addition, the increase trend was found only in patients with lower baseline level of ferritin (≤500 ng/mL) and TSAT (<30%). Conclusions Ferric citrate is an effective phosphate binder with favorable safety profile in ESRD patients. The iron-repletion by ferric citrate is effective, and the increase is limited in patients with a higher baseline. In addition to controlling hyperphosphatemia, ferric citrate also shows additional benefits in the treatment of renal anemia. Clinical trial registration ClinicalTrials.gov ID: NCT03256838; 12/04/2017.
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Affiliation(s)
- Chien-Te Lee
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang-Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan City, Taiwan
| | - Chin-Chan Lee
- Division of Nephrology, Department of Internal Medicine, Keelung Chang-Gung Memorial Hospital, Keelung City, Taiwan
| | - Ming-Ju Wu
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan
| | - Yi-Wen Chiu
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan
| | - Jyh-Gang Leu
- Division of Nephrology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Ming-Shiou Wu
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Yu-Sen Peng
- Division of Nephrology, Department of Internal Medicine, Far-Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Mai-Szu Wu
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
- Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, New Taipei City, Taiwan
- TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan
- * E-mail: (MSW); (DCT)
| | - Der-Cherng Tarng
- Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- * E-mail: (MSW); (DCT)
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24
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Deschner M, Vasanthamohan L, Zayed S, Lazo-Langner A, Palma D, D'Souza D, Omar Gilani S, Gabriel Boldt R, Solh Z. The impact of red blood cell transfusion on mortality and treatment efficacy in patients treated with radiation: A systematic review. Clin Transl Radiat Oncol 2022; 33:23-29. [PMID: 35243018 PMCID: PMC8885402 DOI: 10.1016/j.ctro.2021.12.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 12/02/2021] [Accepted: 12/05/2021] [Indexed: 11/25/2022] Open
Abstract
Higher hemoglobin (Hb) levels may improve outcomes in radiation therapy (RT). There are no standard red blood cell transfusion thresholds for RT patients. We found no differences between standard and higher Hb thresholds during RT. Data is lacking on the effects of transfusion strategies in patients undergoing RT. Introduction Packed red blood cell (RBC) transfusion is frequently used in patients undergoing radiotherapy (RT) because retrospective data suggest that anemic patients may respond sub-optimally to RT. No high-quality evidence currently exists to guide transfusion practices and establish hemoglobin (Hb) transfusion thresholds for this patient population, and practice varies significantly across centers. This systematic review investigated whether maintaining higher Hb via transfusion in radiation oncology patients leads to improved outcomes. Methods We performed a literature search of studies comparing RBC transfusion thresholds in radiation oncology patients. Included studies assessed patients receiving RT for malignancy of any diagnosis or stage. Excluded studies did not evaluate Hb or transfusion as an intervention or outcome. The primary outcome was overall survival. Secondary outcomes included locoregional control, number of transfusions and adverse events. Results One study met inclusion criteria. The study pooled results from two randomized controlled trials that stratified anemic patients with head and neck squamous cell carcinoma to RBC transfusion versus no transfusion. The study found no significant differences in overall survival or locoregional control after five years, despite increased Hb levels in the transfused group. We conducted a narrative review by extracting data from 10 non-comparative studies involving transfusion in patients receiving RT. Results demonstrated no consistent conclusions regarding whether transfusions improve or worsen outcomes. Conclusions There is a lack of data on the effects of RBC transfusion on outcomes in patients undergoing RT. Well-designed prospective studies are needed in this area.
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25
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Onconephrology. Pediatr Nephrol 2022. [DOI: 10.1007/978-3-030-52719-8_122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
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Hassanain WA, Theiss FL, Izake EL. Label-free identification of Erythropoietin isoforms by surface enhanced Raman spectroscopy. Talanta 2022; 236:122879. [PMID: 34635259 DOI: 10.1016/j.talanta.2021.122879] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Revised: 09/05/2021] [Accepted: 09/10/2021] [Indexed: 01/21/2023]
Abstract
We present a sensitive label-free surface enhanced Raman spectroscopy (SERS) method for the discrimination between the recombinant and endogenous human Erythropoietin (EPO) isoforms. The proposed methodology comprises a lectin-functionalised extractor chip for the extraction of the recombinant human EPO (rhuEPO) and the endogenous EPO (enEPO) from blood plasma. The disulfide bond molecular structure of the purified isoforms was modified to chemisorb the biomolecules onto a SERS substrate in a unified orientation, thus maximizing the reproducibility and sensitivity of the SERS measurements. The acquired SERS spectra of the EPO isoforms showed diagnostic Raman bands that allowed for the discrimination between rhuEPO and enEPO. The method was also used for the SERS quantification of rhuEPO and enEPO down to 0.1 pM and 0.5 pM, respectively. The SERS determination of the protein isoforms was cross validated against ELISA. The new SERS method has strong potential for the rapid screening of rhuEPO doping in athletes and for the therapeutic drug monitoring of rhuEPO treatment in cancer patients.
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Affiliation(s)
- Waleed A Hassanain
- School of Chemistry and Physics, Faculty of Science, Queensland University of Technology, 2 George Street, Brisbane, 4001, Australia
| | - Frederick L Theiss
- School of Chemistry and Physics, Faculty of Science, Queensland University of Technology, 2 George Street, Brisbane, 4001, Australia
| | - Emad L Izake
- School of Chemistry and Physics, Faculty of Science, Queensland University of Technology, 2 George Street, Brisbane, 4001, Australia.
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27
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Makharadze T, Boccia R, Krupa A, Blackman N, Henry DH, Gilreath JA. Efficacy and safety of ferric carboxymaltose infusion in reducing anemia in patients receiving chemotherapy for nonmyeloid malignancies: A randomized, placebo-controlled study (IRON-CLAD). Am J Hematol 2021; 96:1639-1646. [PMID: 34653287 PMCID: PMC9298873 DOI: 10.1002/ajh.26376] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 09/30/2021] [Accepted: 10/04/2021] [Indexed: 12/03/2022]
Abstract
Erythropoiesis‐stimulating agents (ESA) are effective for chemotherapy‐induced anemia (CIA) but associated with serious adverse events. Safer alternatives would be beneficial in this population. The efficacy and safety of ferric carboxymaltose (FCM) as monotherapy for CIA was evaluated. This Phase 3, 18‐week, double‐blind, placebo‐controlled study randomized adults with ≥ 4 weeks of chemotherapy remaining for treatment of nonmyeloid malignancies with CIA to FCM (two 15 mg/kg infusions 7 days apart; maximum dose, 750 mg single/1500 mg total) or placebo. The primary efficacy endpoint was percentage of patients with decreases in hemoglobin (Hb) ≥ 0.5 g/dL from weeks 3 to 18; the key secondary efficacy endpoint was change in Hb from baseline to week 18. Inclusion criteria included: (Hb) 8–11 g/dL, ferritin 100–800 ng/mL, and transferrin saturation (TSAT) ≤35%. In 244 patients (n = 122, both groups), the percent of patients who maintained Hb within 0.5 g/dL of baseline from weeks 3 to 18 was significantly higher with FCM versus placebo (50.8% vs. 35.3%; p = 0.01). Mean change in Hb from baseline to week 18 was similar between FCM and placebo (1.04 vs. 0.87 g/dL) but significantly greater with FCM with baseline Hb ≤ 9.9 g/dL (1.08 vs. 0.42 g/dL; p = 0.01). The percent with ≥ 1 g/dL increase from baseline was significantly higher with FCM versus placebo (71% vs. 54%; p = 0.01), occurring in a median 43 versus 85 days (p = 0.001). Common adverse events in the FCM arm included neutropenia (17%), hypophosphatemia (16%), and fatigue (15%). FCM monotherapy effectively maintained Hb and was well tolerated in CIA.
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Affiliation(s)
| | - Ralph Boccia
- Center for Cancer and Blood Disorders Bethesda Maryland USA
| | - Anna Krupa
- College of Pharmacy and Health Sciences St. John's University Queens New York USA
| | | | - David H. Henry
- Abramson Cancer Center Pennsylvania Hospital Philadelphia Pennsylvania USA
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28
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Bojesen RD, Eriksen JR, Vogelsang RP, Grube C, Forman JL, Gogenür I. The dynamic effects of preoperative intravenous iron in anaemic patients undergoing surgery for colorectal cancer. Colorectal Dis 2021; 23:2550-2558. [PMID: 34166572 DOI: 10.1111/codi.15789] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 06/02/2021] [Accepted: 06/18/2021] [Indexed: 12/21/2022]
Abstract
AIM The aim of this study was to describe the dynamic changes in blood work following individual adjusted dosage of intravenously administered iron(III) isomaltoside in a 4-week period prior to surgery in patients with colorectal cancer. METHODS This was a single-centre, observational cohort study with prospectively collected data, including patients with colorectal cancer receiving preoperative treatment with iron(III) isomaltoside. Blood samples were taken at baseline, 1 week, 2 weeks and 4 weeks after initial treatment. Sixty-two patients were included in the study. RESULTS Sixty-two patients were included for final analysis. The mean increase in haemoglobin was 0.77 g/dl (95% CI 0.52-1.03 g/dl, P < 0.0001) at week 1, 1.5 g/dl (95% CI 1.21-1.80 g/dl, P < 0.0001) at week 2 and 2.13 g/dl (95% CI 1.71-2.55 g/dl, P < 0.0001) at week 4. Patients with severe anaemia (<9.02 g/dl) showed the largest increase in haemoglobin during the treatment course (2.92 g/dl, 95% CI 2.27-3.58 g/dl, P < 0.0001). Patients with mild anaemia (>10.31 g/dl) did not show a significant increase (0.66 g/dl, 95% CI -0.29-1.61 g/dl, P = 0.17). The mean of transferrin saturation after 4 weeks was 8% (95% CI 6%-10%, P < 0.0001). CONCLUSIONS After intravenously administered iron, patients with severe anaemia had the most substantial increase in haemoglobin, and the increase was largest after 4 weeks. Patients with mild anaemia did not have an increase in haemoglobin during the treatment course. The vast majority of patients still had iron deficiency at surgery 4 weeks after the initial treatment.
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Affiliation(s)
- Rasmus Dahlin Bojesen
- Department of Surgery, Slagelse Hospital, Slagelse, Denmark.,Centre for Surgical Science, Zealand University Hospital, Køge, Denmark
| | | | | | - Camilla Grube
- Department of Surgery, Slagelse Hospital, Slagelse, Denmark.,Centre for Surgical Science, Zealand University Hospital, Køge, Denmark
| | - Julie Lyng Forman
- Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Ismail Gogenür
- Centre for Surgical Science, Zealand University Hospital, Køge, Denmark
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29
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Shi L, Wang Y, Li L, Chou D, Zhao Y, Zhang S, Wang L, Zhang M, Liu Y. Prognostic value of pretreatment anemia in patients with soft tissue sarcoma: A meta-analysis. Medicine (Baltimore) 2021; 100:e27221. [PMID: 34664860 PMCID: PMC8448052 DOI: 10.1097/md.0000000000027221] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Accepted: 06/23/2021] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Anemia is one of the most common manifestations in patients with cancer. Recently, multiple studies have shown a positive correlation between pretreatment anemia and tumor prognosis. Yet, the relationship between pretreatment anemia and the prognosis of soft tissue sarcomas (STS) is unclear. METHODS We searched the PubMed and EMBASE databases to identify relevant studies. Eligible studies were included according to the inclusion criteria to assess the relationship between pretreatment anemia and the prognosis of patients with STS. Prognostic significance was determined by studying hazard ratios (HR) and 95% confidence intervals (CIs). RESULTS A total of 12 studies are included. If there is significant heterogeneity, a random-effects model is used. Pooled data indicated that pretreatment anemia is related to poor overall survival (HR = 2.13; 95%CI = 1.52-2.98), disease-specific survival (HR = 1.53; 95%CI = 1.20-1.96), and disease-free survival (HR = 1.55; 95%CI = 1.10-2.17). The results of the subgroup analysis also support this conclusion. CONCLUSION Our results suggest that pretreatment anemia may be a prognostic biomarker for STS.
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Affiliation(s)
- Landa Shi
- Department of Orthopedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Yuqiang Wang
- Department of Orthopedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Longqing Li
- Department of Orthopedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Dean Chou
- Department of Neurosurgery, University of California San Francisco, San Francisco, CA
| | - Yao Zhao
- Department of Orthopedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Shuhao Zhang
- Department of Orthopedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Limin Wang
- Department of Orthopedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Min Zhang
- Department of Orthopedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Yilin Liu
- Department of Orthopedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
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30
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Wu CT, Tsai YT, Jung HK, Fu SL, Hsiung CA, Liu HY, Lai JN. Metformin and the Risk of Anemia of Advanced Chronic Kidney Disease in Patients With Type 2 Diabetes Mellitus. J Clin Pharmacol 2021; 62:276-284. [PMID: 34510471 DOI: 10.1002/jcph.1965] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 09/07/2021] [Indexed: 11/06/2022]
Abstract
This retrospective cohort study determines whether metformin monotherapy or combination therapies can decrease anemia risk in the progress of advanced chronic kidney disease for patients with type 2 diabetes mellitus. The data set was obtained from the National Health Insurance Research Database, containing 1 million randomly selected beneficiaries. After matching, 9303 pairs (1:1) of metformin users and nonusers were acquired. Every patient was individually recorded from 1997 to 2012 to identify anemia incidence (hemoglobin <9 gm/dL). Cox regression models were used to compute hazard ratios and 95% confidence intervals (CIs). There were 305 (0.7%) and 76 (0.8%) erythropoietin-stimulating agent cases in the metformin and non-metformin cohorts over a mean follow-up period of 6.8 and 5.6 years. After matching, the use of metformin decreased the risk of usage of erythropoietin-stimulating agents with an adjusted hazard ratio of 0.76 (95%CI, 0.45-1.29) for dosage of <357 g to 0.30 (95%CI, 0.17-0.56) for >1368 g. The combination of metformin and dipeptidyl peptidase-4 inhibitors decreased with a hazard ratio of 0.42 (95%CI, 0.18-0.99), compared to metformin alone. Metformin combined with dipeptidyl peptidase-4 inhibitors is superior to metformin monotherapy or non-metformin antidiabetic therapies for reducing the risk of anemia in the progress of advanced chronic kidney disease among patients with type 2 diabetes.
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Affiliation(s)
- Chien-Tung Wu
- Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Chinese Medicine, Taipei City Hospital, Taipei, Taiwan
| | - Yueh-Ting Tsai
- School of Post Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan.,Department of Traditional Chinese Medicine, Kuang Tien General Hospital, Taichung, Taiwan
| | - Hsuan-Kuang Jung
- Department of Internal Medicine and Nephrology, Taipei City Hospital Yangming Branch, Taipei, Taiwan.,School of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Shu-Ling Fu
- Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chao Agnes Hsiung
- Institute of Population Health Sciences, National Health Research Institutes, Taiwan
| | - Hsiao-Yu Liu
- Institute of Population Health Sciences, National Health Research Institutes, Taiwan
| | - Jung-Nien Lai
- Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan.,Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
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31
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Furrer R, Jauch AJ, Nageswara Rao T, Dilbaz S, Rhein P, Steurer SA, Recher M, Skoda RC, Handschin C. Remodeling of metabolism and inflammation by exercise ameliorates tumor-associated anemia. SCIENCE ADVANCES 2021; 7:eabi4852. [PMID: 34516881 PMCID: PMC8442918 DOI: 10.1126/sciadv.abi4852] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 07/15/2021] [Indexed: 05/30/2023]
Abstract
A considerable number of patients with cancer suffer from anemia, which has detrimental effects on quality of life and survival. The mechanisms underlying tumor-associated anemia are multifactorial and poorly understood. Therefore, we aimed at systematically assessing the patho-etiology of tumor-associated anemia in mice. We demonstrate that reduced red blood cell (RBC) survival rather than altered erythropoiesis is driving the development of anemia. The tumor-induced inflammatory and metabolic remodeling affect RBC integrity and augment splenic phagocyte activity promoting erythrophagocytosis. Exercise training normalizes these tumor-associated abnormal metabolic profiles and inflammation and thereby ameliorates anemia, in part, by promoting RBC survival. Fatigue was prevented in exercising tumor-bearing mice. Thus, exercise has the unique potential to substantially modulate metabolism and inflammation and thereby counteracts pathological remodeling of these parameters by the tumor microenvironment. Translation of this finding to patients with cancer could have a major impact on quality of life and potentially survival.
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Affiliation(s)
| | - Annaïse J. Jauch
- Immunodeficiency Laboratory, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
| | - Tata Nageswara Rao
- Experimental Hematology, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
| | - Sedat Dilbaz
- Biozentrum, University of Basel, Basel, Switzerland
| | | | | | - Mike Recher
- Immunodeficiency Laboratory, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
| | - Radek C. Skoda
- Experimental Hematology, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
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32
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Wu NL, Hingorani S. Outcomes of kidney injury including dialysis and kidney transplantation in pediatric oncology and hematopoietic cell transplant patients. Pediatr Nephrol 2021; 36:2675-2686. [PMID: 33411070 PMCID: PMC11198913 DOI: 10.1007/s00467-020-04842-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 09/10/2020] [Accepted: 10/22/2020] [Indexed: 01/26/2023]
Abstract
Pediatric oncology and hematopoietic cell transplant (HCT) patients are susceptible to both acute kidney injury (AKI) and chronic kidney disease (CKD). The etiologies of AKI vary but include tumor infiltration, radiation, drug-induced toxicity, and fluid and electrolyte abnormalities including tumor lysis syndrome. HCT patients can also have additional complications such as sinusoidal obstructive syndrome, graft-versus-host disease, or thrombotic microangiopathy. For patients with severe AKI requiring dialysis, multiple modalities can be used successfully, although continuous kidney replacement therapy (CKRT) is often the principal modality for critically ill patients. While increasing numbers of pediatric cancer and HCT patients are now surviving long term, they remain at risk for a number of chronic medical conditions, including CKD. Certain high-risk patients, due to underlying risk factors or treatment-related complications, eventually develop kidney failure and may require kidney replacement therapies. Management of co-morbidities and complications associated with kidney failure, including use of erythropoietin for anemia and potential need for ongoing cancer-related treatment while on dialysis, is an additional consideration in this patient population. Kidney transplantation can be successfully performed in pediatric cancer survivors, although additional features such as specific cancer diagnosis and duration of remission should be considered.
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Affiliation(s)
- Natalie L Wu
- Department of Pediatrics, Division of Hematology/Oncology, Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, University of Washington School of Medicine, 4800 Sand Point Way NE, Seattle, WA, 98105, USA
| | - Sangeeta Hingorani
- Department of Pediatrics, Division of Nephrology, Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, University of Washington School of Medicine, 4800 Sand Point Way NE, Seattle, WA, 98105, USA.
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33
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Sawayama H, Miyamoto Y, Mima K, Kato R, Ogawa K, Hiyoshi Y, Shimokawa M, Akiyama T, Kiyozumi Y, Iwagami S, Iwatsuki M, Baba Y, Yoshida N, Baba H. Preoperative iron status is a prognosis factor for stage II and III colorectal cancer. Int J Clin Oncol 2021; 26:2037-2045. [PMID: 34302234 DOI: 10.1007/s10147-021-01995-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 07/19/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Iron deficiency anemia is represented in colorectal cancer (CRC) patients. Iron surplus load to increase non-transferrin bound iron (NTBI), and NTBI promotes cancer progression and influences microbiota. This study investigated whether preoperative serum iron status was associated with prognosis after CRC resection. METHODS We evaluated preoperative iron and transferrin saturation (TSAT), which was calculated as iron divided by total iron-binding capacity, in 327 patients who underwent surgery for Stage II-III CRC. Fe < 60 μg/dl and TSAT > 40% were defined as low and high iron, respectively. The associations between iron status and overall survival (OS) were evaluated in univariate and multivariate Cox proportional hazards analysis. RESULTS Of the 327 patients, 179 (54.7%), 124 (37.9%) and 24 (7.3%) had low, normal and high iron, respectively. In univariate analysis, low iron was associated with shorter OS (hazard ratio [HR] 2.821, 95% confidence interval [CI] 1.451-5.485, P = 0.002). High iron was also associated with shorter OS (HR 3.396, 95% CI 1.359-8.489, P = 0.009). In multivariate analysis, high age (P = 0.002), depth of invasion pT4 (P = 0.012), lymph-node metastasis presence (P = 0.035), low albumin (P = 0.011), low iron (HR 2.282, 95% CI 1.163-4.478, P = 0.016) and high iron (HR 3.757, 95% CI 1.486-9.494 P = 0.005) were independently associated with shorter OS. High iron was associated with the amount of intratumoral Fusobacterium nucleatum compared with normal iron. CONCLUSION Both low and high preoperative iron in Stage II-III CRC patients were associated with unfavorable OS in univariate and multivariate analyses.
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Affiliation(s)
- Hiroshi Sawayama
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Yuji Miyamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Kosuke Mima
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Rikako Kato
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Katsuhiro Ogawa
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Yukiharu Hiyoshi
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo, 135-8550, Japan
| | - Mototsugu Shimokawa
- Department of Biostatistics, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan
| | - Takahiko Akiyama
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Yuki Kiyozumi
- Department of Biostatistics, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan
| | - Shiro Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Masaaki Iwatsuki
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Yoshifumi Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Naoya Yoshida
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
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34
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Madeddu C, Neri M, Sanna E, Oppi S, Macciò A. Experimental Drugs for Chemotherapy- and Cancer-Related Anemia. J Exp Pharmacol 2021; 13:593-611. [PMID: 34194245 PMCID: PMC8238072 DOI: 10.2147/jep.s262349] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 04/21/2021] [Indexed: 01/03/2023] Open
Abstract
Anemia in cancer patients is a relevant condition complicating the course of the neoplastic disease. Overall, we distinguish the anemia which arises under chemotherapy as pure adverse event of the toxic effects of the drugs used, and the anemia induced by the tumour-associated inflammation, oxidative stress, and systemic metabolic changes, which can be worsened by the concomitant anticancer treatments. This more properly cancer-related anemia depends on several overlapping mechanism, including impaired erythropoiesis and functional iron deficiency, which make its treatment more difficult. Standard therapies approved and recommended for cancer anemia, as erythropoiesis-stimulating agents and intravenous iron administration, are limited to the treatment of chemotherapy-induced anemia, preferably in patients with advanced disease, in view of the still unclear effect of erythropoiesis-stimulating agents on tumour progression and survival. Outside the use of chemotherapy, there are no recommendations for the treatment of cancer-related anemia. For a more complete approach, it is fundamentally a careful evaluation of the type of anemia and iron homeostasis, markers of inflammation and changes in energy metabolism. In this way, anemia management in cancer patient would permit a tailored approach that could give major benefits. Experimental drugs targeting hepcidin and activin II receptor pathways are raising great expectations, and future clinical trials will confirm their role as remedies for cancer-related anemia. Recent evidence on the effect of integrated managements, including nutritional support, antioxidants and anti-inflammatory substances, for the treatment of cancer anemia are emerging. In this review article, we show standard, innovative, and experimental treatment used as remedy for anemia in cancer patients.
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Affiliation(s)
- Clelia Madeddu
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Manuela Neri
- Department of Gynecologic Oncology, A. Businco Hospital, ARNAS G. Brotzu, Cagliari, Italy
| | - Elisabetta Sanna
- Department of Gynecologic Oncology, A. Businco Hospital, ARNAS G. Brotzu, Cagliari, Italy
| | - Sara Oppi
- Hematology and Transplant Center, A. Businco Hospital, ARNAS G. Brotzu, Cagliari, Italy
| | - Antonio Macciò
- Department of Gynecologic Oncology, A. Businco Hospital, ARNAS G. Brotzu, Cagliari, Italy
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35
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Obi Y, Ichimaru N, Sakaguchi Y, Iwadoh K, Ishii D, Sakai K, Iwami D, Harada H, Sumida K, Sekine A, Masutani K, Akutsu N, Inoue T, Nishihira M, Yoneda T, Ito S, Araki M, Kaimori JY, Yoshida K, Satoh S, Ubara Y, Isaka Y, Yoshida K, Tsubakihara Y, Takahara S, Hamano T. Correcting anemia and native vitamin D supplementation in kidney transplant recipients: a multicenter, 2 × 2 factorial, open-label, randomized clinical trial. Transpl Int 2021; 34:1212-1225. [PMID: 33884674 DOI: 10.1111/tri.13885] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 03/10/2021] [Accepted: 04/03/2021] [Indexed: 12/21/2022]
Abstract
Anemia and vitamin D deficiency are associated with allograft failure, and hence, are potential therapeutic targets among kidney transplant recipients (KTRs). We conducted a multicenter, two-by-two factorial, open-label, randomized clinical trial to examine the effects of anemia correction and vitamin D supplementation on 2-year change in eGFR among KTRs (CANDLE-KIT). We enrolled 153 patients with anemia and >1-year history of transplantation across 23 facilities in Japan, and randomly assigned them to either a high or low hemoglobin target (>12.5 vs. <10.5 g/dl) and to either cholecalciferol 1000 IU/day or control. This trial was terminated early based on the planned interim intention-to-treat analyses (α = 0.034). Among 125 patients who completed the study, 2-year decline in eGFR was smaller in the high vs. low hemoglobin group (i.e., -1.6 ± 4.5 vs. -4.0 ± 6.9 ml/min/1.73 m2 ; P = 0.021), but did not differ between the cholecalciferol and control groups. These findings were supported by the fully adjusted mixed effects model evaluating the rate of eGFR decline among all 153 participants. There were no significant between-group differences in all-cause death or the renal composite outcome in either arm. In conclusion, aggressive anemia correction showed a potential to preserve allograft kidney function.
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Affiliation(s)
- Yoshitsugu Obi
- Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Japan.,Obi Clinic, Osaka, Japan.,Division of Nephrology, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Naotsugu Ichimaru
- Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Suita, Japan
| | - Yusuke Sakaguchi
- Department of Inter-Organ Communication Research in Kidney Disease, Osaka University Graduate School of Medicine, Suita, Japan
| | - Kazuhiro Iwadoh
- Department of Surgery III, Tokyo Women's Medical University, Tokyo, Japan.,Department of Blood Purification, Tokyo Women's Medical University, Tokyo, Japan
| | - Daisuke Ishii
- Department of Urology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Ken Sakai
- Department of Nephrology, Omori Medical Center, Toho University School of Medicine, Tokyo, Japan
| | - Daiki Iwami
- Department of Urology, Hokkaido University, Sapporo, Japan.,Division of Renal Surgery and Transplantation, Department of Urology, Jichi Medical University, Shimotsuke, Japan
| | - Hiroshi Harada
- Department of Kidney Transplant Surgery, Sapporo City General Hospital, Sapporo, Japan
| | - Keiichi Sumida
- Division of Nephrology, University of Tennessee Health Science Center, Memphis, TN, USA.,Nephrology Center, Toranomon Hospital Kajigaya, Kawasaki, Japan
| | - Akinari Sekine
- Nephrology Center, Toranomon Hospital Kajigaya, Kawasaki, Japan
| | - Kosuke Masutani
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Naotake Akutsu
- Department of Surgery and Clinical Research Center, Chibahigashi National Hospital, National Hospital Organization, Chiba, Japan
| | - Takamitsu Inoue
- Department of Urology, Akita University Graduate School of Medicine, Akita, Japan
| | | | - Tatsuo Yoneda
- Departments of Urology, Nara Medical University, Kashihara, Nara, Japan
| | | | - Motoo Araki
- Department of Urology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Jun-Ya Kaimori
- Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Suita, Japan.,Department of Inter-Organ Communication Research in Kidney Disease, Osaka University Graduate School of Medicine, Suita, Japan
| | - Katsunori Yoshida
- Departments of Urology, Nara Medical University, Kashihara, Nara, Japan
| | - Shigeru Satoh
- Center for Kidney Disease and Transplantation, Akita University Hospital, Akita, Japan
| | - Yoshifumi Ubara
- Nephrology Center, Toranomon Hospital Kajigaya, Kawasaki, Japan
| | - Yoshitaka Isaka
- Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Kazunari Yoshida
- Department of Urology, Kitasato University School of Medicine, Sagamihara, Japan.,Research and Development Center for New Medical Frontiers, Organ Transplant Medicine, Kitasato University School of Medicine, Sagamihara, Japan
| | - Yoshiharu Tsubakihara
- Department of Safety Management in Health Care Sciences, Graduate School of Health Care Sciences, Jikei Institute, Osaka, Japan
| | - Shiro Takahara
- Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Suita, Japan.,Department of Renal Transplantation, Kansai Medical Hospital, Toyonaka, Japan
| | - Takayuki Hamano
- Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Japan.,Department of Inter-Organ Communication Research in Kidney Disease, Osaka University Graduate School of Medicine, Suita, Japan.,Department of Nephrology, Graduate School of Medical Science, Nagoya City University, Nagoya, Japan
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36
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Geng G, Liu J, Xu C, Pei Y, Chen L, Mu C, Wang D, Gao J, Li Y, Liang J, Zhao T, Zhang C, Zhou J, Chen Q, Zhu Y, Shi L. Receptor-mediated mitophagy regulates EPO production and protects against renal anemia. eLife 2021; 10:64480. [PMID: 33942716 PMCID: PMC8121547 DOI: 10.7554/elife.64480] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Accepted: 05/02/2021] [Indexed: 12/14/2022] Open
Abstract
Erythropoietin (EPO) drives erythropoiesis and is secreted mainly by the kidney upon hypoxic or anemic stress. The paucity of EPO production in renal EPO-producing cells (REPs) causes renal anemia, one of the most common complications of chronic nephropathies. Although mitochondrial dysfunction is commonly observed in several renal and hematopoietic disorders, the mechanism by which mitochondrial quality control impacts renal anemia remains elusive. In this study, we showed that FUNDC1, a mitophagy receptor, plays a critical role in EPO-driven erythropoiesis induced by stresses. Mechanistically, EPO production is impaired in REPs in Fundc1-/- mice upon stresses, and the impairment is caused by the accumulation of damaged mitochondria, which consequently leads to the elevation of the reactive oxygen species (ROS) level and triggers inflammatory responses by up-regulating proinflammatory cytokines. These inflammatory factors promote the myofibroblastic transformation of REPs, resulting in the reduction of EPO production. We therefore provide a link between aberrant mitophagy and deficient EPO generation in renal anemia. Our results also suggest that the mitochondrial quality control safeguards REPs under stresses, which may serve as a potential therapeutic strategy for the treatment of renal anemia.
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Affiliation(s)
- Guangfeng Geng
- State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin, China
| | - Jinhua Liu
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Changlu Xu
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Yandong Pei
- State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin, China
| | - Linbo Chen
- State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin, China
| | - Chenglong Mu
- State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin, China
| | - Ding Wang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Jie Gao
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Yue Li
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Jing Liang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Tian Zhao
- State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin, China
| | - Chuanmei Zhang
- State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin, China
| | - Jiaxi Zhou
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Quan Chen
- State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin, China
| | - Yushan Zhu
- State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin, China
| | - Lihong Shi
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
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37
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Thiruthaneeswaran N, Bibby BAS, Yang L, Hoskin PJ, Bristow RG, Choudhury A, West C. Lost in application: Measuring hypoxia for radiotherapy optimisation. Eur J Cancer 2021; 148:260-276. [PMID: 33756422 DOI: 10.1016/j.ejca.2021.01.039] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 01/21/2021] [Accepted: 01/28/2021] [Indexed: 12/15/2022]
Abstract
The history of radiotherapy is intertwined with research on hypoxia. There is level 1a evidence that giving hypoxia-targeting treatments with radiotherapy improves locoregional control and survival without compromising late side-effects. Despite coming in and out of vogue over decades, there is now an established role for hypoxia in driving molecular alterations promoting tumour progression and metastases. While tumour genomic complexity and immune profiling offer promise, there is a stronger evidence base for personalising radiotherapy based on hypoxia status. Despite this, there is only one phase III trial targeting hypoxia modification with full transcriptomic data available. There are no biomarkers in routine use for patients undergoing radiotherapy to aid management decisions, and a roadmap is needed to ensure consistency and provide a benchmark for progression to application. Gene expression signatures address past limitations of hypoxia biomarkers and could progress biologically optimised radiotherapy. Here, we review recent developments in generating hypoxia gene expression signatures and highlight progress addressing the challenges that must be overcome to pave the way for their clinical application.
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Affiliation(s)
- Niluja Thiruthaneeswaran
- Division of Cancer Sciences, The University of Manchester, Manchester, UK; Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
| | - Becky A S Bibby
- Division of Cancer Sciences, The University of Manchester, Manchester, UK
| | - Lingjang Yang
- Division of Cancer Sciences, The University of Manchester, Manchester, UK
| | - Peter J Hoskin
- Division of Cancer Sciences, The University of Manchester, Manchester, UK; Mount Vernon Cancer Centre, Northwood, UK
| | - Robert G Bristow
- Division of Cancer Sciences, The University of Manchester, Manchester, UK; CRUK Manchester Institute and Manchester Cancer Research Centre, Manchester, UK
| | - Ananya Choudhury
- Division of Cancer Sciences, The University of Manchester, Christie Hospital NHS Foundation Trust, Manchester, UK
| | - Catharine West
- Division of Cancer Sciences, The University of Manchester, Christie Hospital NHS Foundation Trust, Manchester, UK
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38
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Raichoudhury R, Spinowitz BS. Treatment of anemia in difficult-to-manage patients with chronic kidney disease. Kidney Int Suppl (2011) 2021; 11:26-34. [PMID: 33777493 DOI: 10.1016/j.kisu.2020.12.006] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 12/17/2020] [Accepted: 12/29/2020] [Indexed: 12/14/2022] Open
Abstract
The management of anemia of chronic kidney disease (CKD) is often challenging. In particular, for patients with underlying inflammation, comorbid type 2 diabetes or cancer, those hospitalized, and recipients of a kidney transplant, the management of anemia may be suboptimal. Responsiveness to iron and/or erythropoiesis-stimulating agents, the mainstay of current therapy, may be reduced and the risk of adverse reactions to treatment is increased in these difficult-to-manage patients with anemia of CKD. This review discusses the unique patient and disease characteristics leading to complications and suboptimal treatment response. New treatment options in clinical development, such as hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors, may be particularly useful for difficult-to-treat patients. In clinical studies, HIF-PH inhibitors provided increased hemoglobin levels and improved iron utilization in anemic patients with non-dialysis-dependent and dialysis-dependent CKD, and preliminary data suggest that HIF-PH inhibitors may be equally effective in patients with or without underlying inflammation. The availability of new treatment options, including HIF-PH inhibitors, may improve treatment outcomes in difficult-to-manage patients with anemia of CKD.
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Affiliation(s)
- Ritesh Raichoudhury
- Division of Nephrology, Department of Medicine, NewYork-Presbyterian Queens, New York, New York, USA
| | - Bruce S Spinowitz
- Division of Nephrology, Department of Medicine, NewYork-Presbyterian Queens, New York, New York, USA
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Abstract
Despite increasing use of targeted therapies to treat cancer, anemia remains a common complication of cancer therapy. Physician concerns about the safety of intravenous (IV) iron products and erythropoiesis-stimulating agents (ESAs) have resulted in many patients with cancer receiving no or suboptimal anemia therapy. In this article, we present 4 patient cases that illustrate both common and complex clinical scenarios. We first present a review of erythropoiesis and then describe our approach to cancer-associated anemia by identifying the contributing causes before selecting specific treatments. We summarize clinical trial data affirming the safety and efficacy of currently available IV iron products used to treat cancer-associated anemia and illustrate how we use commonly available laboratory tests to assess iron status during routine patient management. We compare adverse event rates associated with IV iron vs red cell transfusion and discuss using first-line IV iron monotherapy to treat anemic patients with cancer, which decreases the need for ESAs. A possible mechanism behind ESA-induced tumor progression is discussed. Finally, we review the potential of novel therapies such as ascorbic acid, prolyl hydroxylase inhibitors, activin traps, hepcidin, and bone morphogenetic protein antagonists in treating cancer-associated anemia.
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Eswarappa M, Cantarelli C, Cravedi P. Erythropoietin in Lupus: Unanticipated Immune Modulating Effects of a Kidney Hormone. Front Immunol 2021; 12:639370. [PMID: 33796104 PMCID: PMC8007959 DOI: 10.3389/fimmu.2021.639370] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 02/24/2021] [Indexed: 11/24/2022] Open
Abstract
Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease with variable clinical presentation, typically characterized by a relapsing-remitting course. SLE has a multifactorial pathogenesis including genetic, environmental, and hormonal factors that lead to loss of tolerance against self-antigens and autoantibody production. Mortality in SLE patients remains significantly higher than in the general population, in part because of the limited efficacy of available treatments and the associated toxicities. Therefore, novel targeted therapies are urgently needed to improve the outcomes of affected individuals. Erythropoietin (EPO), a kidney-produced hormone that promotes red blood cell production in response to hypoxia, has lately been shown to also possess non-erythropoietic properties, including immunomodulatory effects. In various models of autoimmune diseases, EPO limits cell apoptosis and favors cell clearance, while reducing proinflammatory cytokines and promoting the induction of regulatory T cells. Notably, EPO has been shown to reduce autoimmune response and decrease disease severity in mouse models of SLE. Herein, we review EPO's non-erythropoietic effects, with a special focus on immune modulating effects in SLE and its potential clinical utility.
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Affiliation(s)
- Meghana Eswarappa
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Chiara Cantarelli
- UO Nefrologia, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Paolo Cravedi
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
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Sano Y, Yoshida T, Choo MK, Jiménez-Andrade Y, Hill KR, Georgopoulos K, Park JM. Multiorgan Signaling Mobilizes Tumor-Associated Erythroid Cells Expressing Immune Checkpoint Molecules. Mol Cancer Res 2020; 19:507-515. [PMID: 33234577 DOI: 10.1158/1541-7786.mcr-20-0746] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 10/07/2020] [Accepted: 11/20/2020] [Indexed: 11/16/2022]
Abstract
Hematopoietic-derived cells are integral components of the tumor microenvironment and serve as critical mediators of tumor-host interactions. Host cells derived from myeloid and lymphoid lineages perform well-established functions linked to cancer development, progression, and response to therapy. It is unclear whether host erythroid cells also contribute to shaping the path that cancer can take, but emerging evidence points to this possibility. Here, we show that tumor-promoting environmental stress and tumor-induced hemodynamic changes trigger renal erythropoietin production and erythropoietin-dependent expansion of splenic erythroid cell populations in mice. These erythroid cells display molecular features indicative of an immature erythroid phenotype, such as the expression of both CD71 and TER119 and the retention of intact nuclei, and express genes encoding immune checkpoint molecules. Nucleated erythroid cells with similar properties are present in mouse and human tumor tissues. Antibody-mediated erythropoietin blockade reduces tumor-responsive erythroid cell induction and tumor growth. These findings reveal the potential of tumor-induced erythropoietin and erythroid cells as targets for cancer treatment. IMPLICATIONS: : Our study identifies erythropoietin and erythroid cells as novel players in tumor-host interactions and highlights the involvement of multiorgan signaling events in their induction in response to environmental stress and tumor growth.
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Affiliation(s)
- Yasuyo Sano
- Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
| | - Toshimi Yoshida
- Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts.,International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Min-Kyung Choo
- Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
| | - Yanek Jiménez-Andrade
- Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
| | - Kathryn R Hill
- Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
| | - Katia Georgopoulos
- Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
| | - Jin Mo Park
- Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts.
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Porta C, Bamias A, Danesh FR, Dębska-Ślizień A, Gallieni M, Gertz MA, Kielstein JT, Tesarova P, Wong G, Cheung M, Wheeler DC, Winkelmayer WC, Małyszko J. KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancer. Kidney Int 2020; 98:1108-1119. [PMID: 33126977 DOI: 10.1016/j.kint.2020.06.046] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2019] [Revised: 05/28/2020] [Accepted: 06/10/2020] [Indexed: 12/12/2022]
Abstract
The association between kidney disease and cancer is multifaceted and complex. Persons with chronic kidney disease (CKD) have an increased incidence of cancer, and both cancer and cancer treatments can cause impaired kidney function. Renal issues in the setting of malignancy can worsen patient outcomes and diminish the adequacy of anticancer treatments. In addition, the oncology treatment landscape is changing rapidly, and data on tolerability of novel therapies in patients with CKD are often lacking. Caring for oncology patients has become more specialized and interdisciplinary, currently requiring collaboration among specialists in nephrology, medical oncology, critical care, clinical pharmacology/pharmacy, and palliative care, in addition to surgeons and urologists. To identify key management issues in nephrology relevant to patients with malignancy, KDIGO (Kidney Disease: Improving Global Outcomes) assembled a global panel of multidisciplinary clinical and scientific expertise for a controversies conference on onco-nephrology in December 2018. This report covers issues related to kidney impairment and solid organ malignancies as well as management and treatment of kidney cancer. Knowledge gaps, areas of controversy, and research priorities are described.
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Affiliation(s)
- Camillo Porta
- Department of Internal Medicine and Therapeutics, University of Pavia and Division of Translational Oncology, IRCCS Istituti Clinici Scientifici Maugeri, Pavia, Italy.
| | - Aristotelis Bamias
- Second Propaedeutic Department of Internal Medicine, National and Kapodistrian University of Athens, Greece
| | - Farhad R Danesh
- Section of Nephrology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Alicja Dębska-Ślizień
- Clinical Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdańsk, Gdańsk, Poland
| | - Maurizio Gallieni
- Nephrology and Dialysis Unit, Luigi Sacco Department of Biomedical and Clinical Sciences, Università di Milano, Milan, Italy
| | - Morie A Gertz
- Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Jan T Kielstein
- Medical Clinic V, Nephrology, Rheumatology, Blood Purification, Academic Teaching Hospital Braunschweig, Braunschweig, Germany
| | - Petra Tesarova
- Department of Oncology, 1st Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
| | - Germaine Wong
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, New South Wales, Australia; Sydney School of Public Health, University of Sydney, New South Wales, Australia
| | | | - David C Wheeler
- Department of Renal Medicine, University College London, London, UK; George Institute for Global Health, Sydney, Australia
| | - Wolfgang C Winkelmayer
- Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Jolanta Małyszko
- Department of Nephrology, Dialysis, and Internal Medicine, Medical University of Warsaw, Poland.
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Musio F. Revisiting the treatment of anemia in the setting of chronic kidney disease, hematologic malignancies, and cancer: perspectives with opinion and commentary. Expert Rev Hematol 2020; 13:1175-1188. [PMID: 33028115 DOI: 10.1080/17474086.2020.1830371] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Accepted: 09/27/2020] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Anemia has and will continue to be a central theme in medicine particularly as clinicians are treating a burgeoning population of complex multi-organ system processes. As a result of multiple randomized controlled trials (RCTs), meta-analyses, and societal recommendations overly restrictive paradigms and under-administration of erythropoiesis stimulating agents (ESAs) have likely been followed by clinicians among all specialties. AREAS COVERED A review of anemia in the context of chronic kidney disease, hematologic malignancies, and cancer is presented with focus on the establishment of ESAs as integral in the treatment of anemia. Multiple RCTs and meta-analyses studying the use of ESAs are presented with focus upon their application to clinical practice. A 'compendium' is proffered describing the evolution, establishment, and implications of ESA administration initially among those with CKD with rapid subsequent application to the Hematology-Oncology population of patients. Literature search methodologies have included MEDLINE (1985-2020), PubMed (1996-2020), Cochrane Central Trials (1985-2020), EMBASE (2000-2020), and ClinicalTrials.gov (2000-2020). EXPERT OPINION Upon evaluation of risks and benefits of ESAs focused opinion and commentary is made supporting more liberal use of these agents and strongly suggesting that the current underlying treatment 'pendulum' has perhaps shifted too far to the 'under-treatment' side in many cases.
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Affiliation(s)
- Franco Musio
- Senior Partner, Nephrology Associates of Northern Virginia , VA, Fairfax, Virginia, USA
- Nephrology Division Chief, Inova Fairfax Hospital, Department of Medicine, Falls Church , Virginia, VA, USA
- Associate Professor of Medicine, Virginia Commonwealth University (Inova Fairfax Hospital Campus) , Richmond, Virginia, USA
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Gennigens C, De Cuypere M, Seidel L, Hermesse J, Barbeaux A, Forget F, Albert A, Jerusalem G, Kridelka F. Correlation between hematological parameters and outcome in patients with locally advanced cervical cancer treated by concomitant chemoradiotherapy. Cancer Med 2020; 9:8432-8443. [PMID: 32954675 PMCID: PMC7666723 DOI: 10.1002/cam4.3465] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 08/23/2020] [Accepted: 08/25/2020] [Indexed: 01/28/2023] Open
Abstract
Background Hemoglobin (Hb), white blood cell (WBC), and polymorphonuclear neutrophil (PMN) blood counts may be correlated with outcomes in patients with locally advanced cervical cancer. Methods Hb, WBC, and PMN counts were measured at diagnosis and during concomitant cisplatin‐based chemoradiotherapy (CCRT) in a retrospective sample of 103 patients between 2010 and 2017. Red blood cell (RBC) transfusions were also recorded. The associations between hematological variables and patient overall survival (OS) and recurrence‐free survival (RFS) were assessed by Cox regression models. Results The 3‐year OS and RFS rates were 81.4% and 76.8%, respectively. In addition to tumor size and smoking, OS and RFS were found to be significantly associated with changes in WBC and PMN counts from the first to the last cisplatin cycle. Hb count throughout the treatment and RBC transfusions were not predictive of outcome. Conclusions This study found no association between Hb count or RBC transfusions and outcome. The daily practice of maintaining the Hb count above 12 g/dL during CCRT should be weighed against the potential risks of transfusions. Drops in WBC and PMN counts during treatment positively impacted OS and RFS and could, therefore, serve as biomarkers during CCRT to adapt the follow‐up and consider the need for adjuvant systemic treatments.
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Affiliation(s)
| | | | - Laurence Seidel
- Department of Biostatistics, CHU Liège and Liège University, Liège, Belgium
| | | | | | - Frédéric Forget
- Department of Medical Oncology, Libramont Hospital, Libramont, Belgium
| | - Adelin Albert
- Department of Biostatistics, CHU Liège and Liège University, Liège, Belgium
| | - Guy Jerusalem
- Department of Medical Oncology, CHU Liège and Liège University, Liège, Belgium
| | - Frédéric Kridelka
- Department of Obstetrics and Gynaecology, CHU Liège and Liège University, Liège, Belgium
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Shin HJ, Kim JH, Han SB, Park JH, Jang WY. Allogeneic red blood cell transfusion is an independent risk factor for 1-year mortality in elderly patients undergoing femoral neck fracture surgery: Retrospective study. Medicine (Baltimore) 2020; 99:e21897. [PMID: 32871921 PMCID: PMC7458220 DOI: 10.1097/md.0000000000021897] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Allogeneic red blood cell transfusion (ABT) is 1 of the poor prognostic factors for morbidity and mortality in patients with hip fracture, particularly among elderly patients. This study aimed to investigate the risk factors for ABT and 1-year mortality in elderly patients undergoing surgery for femoral neck fracture.A total of 225 elderly patients who underwent femoral neck fracture surgery between May 2013 and November 2015 at a tertiary medical center were retrospectively recruited. Medical records were analyzed.The median patient age was 80 years and 28.4% were men. A total of 113 patients received ABT (50.2%). Multivariate logistic regression analysis showed that female sex (odds ratio [OR] 2.606, 95% confidence interval [CI] 1.283-5.295, P = .008), malignancy (OR 5.098, 95% CI 1.725-15.061, P = .003), chronic kidney disease stage ≥ 3 (OR 3.258, 95% CI 1.603-6.622, P = .001), and anemia (hemoglobin < 12 g/dL) (OR 4.684, 95% CI 2.230-9.837, P < .001) were significantly associated with ABT. The 1-year mortality rate after surgery was 15.1%. Male sex (OR 2.477, 95% CI 1.101-5.575, P = .028), ABT (OR 2.367, 95% CI 1.036-5.410, P = .041), and intensive care unit admission (OR 5.564, 95% CI 1.457-21.249, P = .012) were significantly associated with 1-year mortality.In this study, underlying comorbidities such as chronic kidney disease and malignancy were associated with ABT. Furthermore, ABT was a significant independent risk factor for 1-year mortality. These findings suggest that underlying comorbidities and the need for ABT should be considered in the risk assessment of elderly patients with femoral neck fracture to improve the outcomes after surgery.
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Affiliation(s)
- Hyeon Ju Shin
- Department of Anesthesiology and Pain Medicine, Korea University College of Medicine
- Korea University Bloodless Medicine Center
| | - Jong Hun Kim
- Korea University Bloodless Medicine Center
- Division of Infectious Diseases, Department of Internal Medicine
| | - Seung-Beom Han
- Korea University Bloodless Medicine Center
- Department of Orthopedic Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Jong Hoon Park
- Korea University Bloodless Medicine Center
- Department of Orthopedic Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Woo Young Jang
- Korea University Bloodless Medicine Center
- Department of Orthopedic Surgery, Korea University College of Medicine, Seoul, Republic of Korea
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Hacein-Bey-Abina S, Estienne M, Bessoles S, Echchakir H, Pederzoli-Ribeil M, Chiron A, Aldaz-Carroll L, Leducq V, Zhang Y, Souyri M, Louache F, Abina AM. Erythropoietin is a major regulator of thrombopoiesis in thrombopoietin-dependent and -independent contexts. Exp Hematol 2020; 88:15-27. [PMID: 32721504 DOI: 10.1016/j.exphem.2020.07.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Revised: 07/18/2020] [Accepted: 07/22/2020] [Indexed: 01/09/2023]
Abstract
Thrombopoietin (TPO), through activation of its cognate receptor Mpl, is the major regulator of platelet production. However, residual platelets observed in TPO- and Mpl-loss-of-function (LOF) mice suggest the existence of an additional factor to TPO in platelet production. As erythropoietin (EPO) exhibited both in vitro megakaryocytic potential, in association with other early-acting cytokines, and in vivo platelet activation activity, we sought to investigate its role in this setting. Here, we used multiple LOF models to decipher the reciprocal role of EPO and TPO in the regulation of platelet production in TPO-LOF and Mpl-LOF mice and of platelet size heterogeneity in wild-type mice. We first identified EPO as the major thrombopoietic factor in the absence of the TPO-Mpl pathway. Based on the study of several mouse models we found that the EPO-EPO receptor pathway acts on late-stage megakaryopoiesis and is responsible for large-sized platelet production, while the TPO-Mpl pathway promotes small-sized platelet production. On the basis of our data, EPO might be used for thrombocytopenia supportive therapy in congenital amegakaryocytopoiesis. Furthermore, as a distribution skewed toward large platelets is an independent risk factor and a poor prognosis indicator in atherothrombosis, the characterization of EPO's role in the production of large-sized platelets, if confirmed in humans, may open new perspectives in the understanding of the role of EPO-induced platelets in atherothrombosis.
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Affiliation(s)
- Salima Hacein-Bey-Abina
- UTCBS CNRS UMR 8258, INSERM U1267, Faculté de Pharmacie de Paris, Université de Paris, Paris, France; Clinical Immunology Laboratory, Groupe Hospitalier Universitaire Paris-Sud, Hôpital Kremlin-Bicêtre, Assistance Publique-Hôpitaux de Paris, Le-Kremlin-Bicêtre, France.
| | | | - Stéphanie Bessoles
- UTCBS CNRS UMR 8258, INSERM U1267, Faculté de Pharmacie de Paris, Université de Paris, Paris, France
| | | | - Magali Pederzoli-Ribeil
- UTCBS CNRS UMR 8258, INSERM U1267, Faculté de Pharmacie de Paris, Université de Paris, Paris, France
| | - Andrada Chiron
- UTCBS CNRS UMR 8258, INSERM U1267, Faculté de Pharmacie de Paris, Université de Paris, Paris, France; Clinical Immunology Laboratory, Groupe Hospitalier Universitaire Paris-Sud, Hôpital Kremlin-Bicêtre, Assistance Publique-Hôpitaux de Paris, Le-Kremlin-Bicêtre, France
| | - Lydia Aldaz-Carroll
- UTCBS CNRS UMR 8258, INSERM U1267, Faculté de Pharmacie de Paris, Université de Paris, Paris, France
| | | | - Yanyan Zhang
- INSERM U1170, CNRS GDR 3697 MicroNiT, Institut Gustave Roussy, Villejuif, France
| | - Michèle Souyri
- INSERM UMRS 1131, Institut Universitaire d'Hématologie, Université Paris Diderot, Hôpital Saint Louis, Paris, France
| | - Fawzia Louache
- INSERM U1170, CNRS GDR 3697 MicroNiT, Institut Gustave Roussy, Villejuif, France; Université Paris-Sud, Orsay, France
| | - Amine M Abina
- UTCBS CNRS UMR 8258, INSERM U1267, Faculté de Pharmacie de Paris, Université de Paris, Paris, France; NOKAD, Evry, France.
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Hoque S, Chen BJ, Schoen MW, Carson KR, Keller J, Witherspoon BJ, Knopf KB, Yang YT, Schooley B, Nabhan C, Sartor O, Yarnold PR, Ray P, Bobolts L, Hrushesky WJ, Dickson M, Bennett CL. End of an era of administering erythropoiesis stimulating agents among Veterans Administration cancer patients with chemotherapy-induced anemia. PLoS One 2020; 15:e0234541. [PMID: 32584835 PMCID: PMC7316310 DOI: 10.1371/journal.pone.0234541] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 04/18/2020] [Indexed: 11/18/2022] Open
Abstract
Erythropoisis stimulating agent (ESA) use was addressed in Food and Drug Administration (FDA) Oncology Drug Advisory Committee (ODAC) meetings between 2004 and 2008. FDA safety-focused regulatory actions occurred in 2007 and 2008. In 2007, black box warnings advised of early death and venous thromboembolism (VTE) risks with ESAs in oncology. In 2010, a Risk Evaluation Strategies (REMS) was initiated, with cancer patient consent that mortality and VTE risks were noted with ESAs. We report warnings and REMS impacts on ESA utilization among Veterans Administration (VA) cancer patients with chemotherapy-induced anemia (CIA). Data were from Veterans Affairs database (2003–2012). Epoetin and darbepoetin use were primary outcomes. Segmented linear regression was used to estimate changes in ESA use levels and trends, clinical appropriateness, and adverse events (VTEs) among chemotherapy-treated cancer patients. To estimate changes in level of drug prescription rate after policy actions, model-specific indicator variables as covariates based on specific actions were included. ESA use fell by 95% and 90% from 2005, for epoetin and darbepoetin, from 22% and 11%, respectively, to 1% and 1%, respectively, among cancer patients with CIA, respectively (p<0.01). Following REMS in 2010, mean hematocrit levels at ESA initiation decreased from 30% to 21% (p<0.01). Black box warnings preceded decreased ESA use among VA cancer patients with CIA. REMS was followed by reduced hematocrit levels at ESA initiation. Our findings contrast with privately- insured and Medicaid insured cancer patient data on chemotherapy-induced anemia where ESA use decreased to 3% to 7% by 2010–2012. By 2012, the era of ESA administration to VA to cancer patients had ended but the warnings remain relevant and significant. In 2019, oncology/hematology national guidelines (ASCO/ASH) recommend that cancer patients with chemotherapy-induced anemia should receive ESAs or red blood cell transfusions after risk-benefit evaluation.
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Affiliation(s)
- Shamia Hoque
- Department of Civil and Environmental Engineering, College of Engineering and Computing, University of South Carolina, Columbia, South Carolina, United States of America
- * E-mail:
| | - Brian J. Chen
- Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, United States of America
| | - Martin W. Schoen
- Department of Medicine, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America
| | - Kenneth R. Carson
- The Washington University School of Medicine and the Saint Louis VA Medical Center, St. Louis, Missouri, United States of America
| | - Jesse Keller
- The Washington University School of Medicine and the Saint Louis VA Medical Center, St. Louis, Missouri, United States of America
| | | | - Kevin B. Knopf
- College of Pharmacy, University of South Carolina, Columbia, South Carolina, United States of America
| | - Y. Tony Yang
- George Washington University, Washington, DC, United States of America
| | - Benjamin Schooley
- Department of Integrated Information Technology, College of Engineering and Computing, University of South Carolina, Columbia, South Carolina, United States of America
| | - Chadi Nabhan
- College of Pharmacy, University of South Carolina, Columbia, South Carolina, United States of America
| | - Oliver Sartor
- Tulane University School of Medicine, New Orleans, Louisiana, United States of America
| | - Paul R. Yarnold
- Medical University of South Carolina, Charleston, South Carolina, United States of America
- College of Pharmacy, University of South Carolina, Columbia, South Carolina, United States of America
| | - Paul Ray
- College of Pharmacy, University of South Carolina, Columbia, South Carolina, United States of America
| | - Laura Bobolts
- Oncology Analytics, Plantation, Florida, United States of America
- College of Pharmacy, Nova Southeastern University, Fort Lauderdale, Florida, United States of America
| | - William J. Hrushesky
- The Washington University School of Medicine and the Saint Louis VA Medical Center, St. Louis, Missouri, United States of America
- Medical University of South Carolina, Charleston, South Carolina, United States of America
- College of Pharmacy, University of South Carolina, Columbia, South Carolina, United States of America
| | - Michael Dickson
- College of Pharmacy, University of South Carolina, Columbia, South Carolina, United States of America
| | - Charles L. Bennett
- College of Pharmacy, University of South Carolina, Columbia, South Carolina, United States of America
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48
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Sbrana A, Antonuzzo A, Brunello A, Petrelli F, Pronzato P, Tralongo A, Turrini M, Zoratto F, Danova M. Management of anemia in patients with cancer: 2019 Italian Association of Medical Oncology (AIOM) guidelines. TUMORI JOURNAL 2020; 106:337-345. [PMID: 32482149 DOI: 10.1177/0300891620921942] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
This article summarizes the latest Italian Medical Oncology Association (AIOM) guidelines on the management of cancer-related and chemotherapy-related anemia with a particular attention to the use of erythropoiesis-stimulating agents and iron supplementation.
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Affiliation(s)
- Andrea Sbrana
- Medical Oncology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.,Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Andrea Antonuzzo
- Medical Oncology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | | | - Fausto Petrelli
- Medical Oncology Unit, ASST Bergamo Ovest, Treviglio, Bergamo, Italy
| | - Paolo Pronzato
- Medical Oncology Unit, AOU San Martino IRCCS IST, Genova, Italy
| | - Antonino Tralongo
- Medical Oncology Unit, Ospedale di Circolo e Fondazione Macchi, Varese, Italy
| | - Marianna Turrini
- Medical Oncology Unit, Ospedale del Valdarno, Santa Maria La Gruccia, Azienda USL Toscana Sud-Est, Montevarchi, Toscana, Italy
| | - Federica Zoratto
- Medical Oncology Unit, Ospedale S. Maria Goretti, Latina, Lazio, Italy
| | - Marco Danova
- Internal Medicine and Medical Oncology, ASST Pavia, Pavia, Lombardia, Italy
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Abstract
Allogeneic blood transfusions (ABTs) are common in patients with cancer. The present study investigated the safety of a restrictive ABT strategy in patients with extremity sarcomas.Patients who underwent operations for extremity bone sarcomas between May 2008 and November 2018 were retrospectively reviewed. Clinical outcomes based on hemoglobin concentrations, postoperative infections, and hospital stay were compared between 20 patients who received liberal ABT (control group) and 19 patients who received restrictive ABT (restrictive group). The rates of distant metastasis and death were compared between the groups.The mean number of ABTs was 3.6 ± 3.8 units in the control group and 0.33 ± 0.74 units in the restrictive group (P < .001). Only 3 of 19 patients received transfusions (2 red cell packs each). The hemoglobin levels tended to fall during the first 3 postoperative days but seemed to stabilize within the first postoperative week in both groups. Postoperative surgical site infections only occurred in the patients who received ABTs regardless of the group. The rates of distant metastasis and death were higher in the control group than in the restrictive group (25.0% vs 15.7% and 10.0% vs 0%, respectively), but the differences were not significant.A restrictive ABT strategy may be safely performed in patients with extremity bone sarcomas depending on the intraoperative status and specific characteristics of each patient.
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Thavarajah S, Choi MJ. The Use of Erythropoiesis-Stimulating Agents in Patients With CKD and Cancer: A Clinical Approach. Am J Kidney Dis 2019; 74:667-674. [DOI: 10.1053/j.ajkd.2019.04.022] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 04/18/2019] [Indexed: 01/13/2023]
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